Exomiser Analysis Results for Anonymous

Analysis Settings

Settings used for this analysis:

---
sample:
  genomeAssembly: "hg38"
  vcf: "/mnt/storage_pool/Genomics/VarXOmics/examples/P00110_11/P00110_11_vep_annotated.biallelic.vcf.gz"
  hpoIds:
  - "HP:0003002"
  - "HP:0006625"
  pedigree: {}
  age: {}
analysis:
  inheritanceModes:
    AUTOSOMAL_RECESSIVE_COMP_HET: 2.0
    MITOCHONDRIAL: 0.2
    AUTOSOMAL_RECESSIVE_HOM_ALT: 0.1
    X_DOMINANT: 0.1
    AUTOSOMAL_DOMINANT: 0.1
    X_RECESSIVE_COMP_HET: 2.0
    X_RECESSIVE_HOM_ALT: 0.1
  frequencySources:
  - "UK10K"
  - "GNOMAD_E_AFR"
  - "GNOMAD_E_AMR"
  - "GNOMAD_E_EAS"
  - "GNOMAD_E_NFE"
  - "GNOMAD_E_SAS"
  - "GNOMAD_G_AFR"
  - "GNOMAD_G_AMR"
  - "GNOMAD_G_EAS"
  - "GNOMAD_G_NFE"
  - "GNOMAD_G_SAS"
  pathogenicitySources:
  - "REMM"
  steps:
  - hiPhivePrioritiser:
      runParams: "human, mouse, fish, ppi"
  - priorityScoreFilter:
      priorityType: "HIPHIVE_PRIORITY"
      minPriorityScore: 0.501
  - failedVariantFilter: {}
  - genePanelFilter:
      geneSymbols:
      - "PERM1"
      - "KIF1B"
      - "MTHFR"
      - "TNFRSF1B"
      - "DHRS3"
      - "PRAMEF18"
      - "NBPF1"
      - "DDOST"
      - "HSPG2"
      - "CRYBG2"
      - "FCN3"
      - "SMPDL3B"
      - "EPB41"
      - "GJB3"
      - "CDCA8"
      - "MPL"
      - "MMACHC"
      - "PCSK9"
      - "HOOK1"
      - "GBP1"
      - "DPYD"
      - "DBT"
      - "COL11A1"
      - "PTPN22"
      - "ANXA9"
      - "TUFT1"
      - "HRNR"
      - "FLG"
      - "SPRR2E"
      - "TPM3"
      - "SPTA1"
      - "KCNJ9"
      - "PEX19"
      - "F5"
      - "QSOX1"
      - "HMCN1"
      - "CDC73"
      - "CFH"
      - "LAMB3"
      - "RD3"
      - "PACC1"
      - "TATDN3"
      - "FLVCR1"
      - "RAB3GAP2"
      - "ITPKB"
      - "MTR"
      - "RYR2"
      - "FH"
      - "NLRP3"
      - "EIPR1"
      - "ZNF513"
      - "SLC3A1"
      - "MCFD2"
      - "MSH2"
      - "NRXN1"
      - "PNO1"
      - "ANXA4"
      - "GGCX"
      - "CHST10"
      - "IL36RN"
      - "GLI2"
      - "BIN1"
      - "LOC124908048"
      - "ZEB2"
      - "NEB"
      - "TANC1"
      - "SCN2A"
      - "SCN9A"
      - "SCN7A"
      - "LRP2"
      - "HOXD10"
      - "HOXD3"
      - "AGPS"
      - "TTN"
      - "STAT1"
      - "CCDC150"
      - "NDUFS1"
      - "FASTKD2"
      - "PLEKHM3"
      - "CFAP65"
      - "SPEG"
      - "OBSL1"
      - "COL4A3"
      - "CHRNG"
      - "UGT1A10"
      - "GAL3ST2"
      - "ITPR1"
      - "CAV3"
      - "VHL"
      - "RAF1"
      - "NUP210"
      - "EOMES"
      - "ACVR2B"
      - "SLC25A38"
      - "VIPR1"
      - "SLC6A20"
      - "ALS2CL"
      - "KIF9"
      - "LAMB2"
      - "DNAH12"
      - "FLNB"
      - "CLDND1"
      - "ZPLD1"
      - "CCDC191"
      - "ZBTB20"
      - "GPR156"
      - "PCCB"
      - "CPA3"
      - "HPS3"
      - "IFT80"
      - "SLC2A2"
      - "MUC4"
      - "LOC112268458"
      - "LOC124900647"
      - "CFAP99"
      - "SH3BP2"
      - "HTT"
      - "WFS1"
      - "SORCS2"
      - "SH3TC1"
      - "DRD5"
      - "TLR1"
      - "SRD5A3"
      - "AMBN"
      - "STBD1"
      - "ARHGAP24"
      - "FAM13A"
      - "SNCA"
      - "BMPR1B"
      - "SLC9B1"
      - "EGF"
      - "MFSD8"
      - "RAB33B"
      - "FHIP1A"
      - "TLR2"
      - "FNIP2"
      - "PALLD"
      - "AGA"
      - "CCT5"
      - "DNAH5"
      - "TRIO"
      - "LIFR"
      - "CARD6"
      - "ITGA2"
      - "ANKRD55"
      - "PDE4D"
      - "GFM2"
      - "PDE8B"
      - "VCAN"
      - "MEF2C"
      - "WDR36"
      - "HSD17B4"
      - "ALDH7A1"
      - "MEGF10"
      - "UQCRQ"
      - "LECT2"
      - "TGFBI"
      - "KLHL3"
      - "HSPA9"
      - "PURA"
      - "PCDHB3"
      - "DIAPH1"
      - "SH3TC2"
      - "PDE6A"
      - "PDGFRB"
      - "SLU7"
      - "ATP10B"
      - "SH3PXD2B"
      - "FGFR4"
      - "WRNIP1"
      - "F13A1"
      - "DSP"
      - "DTNBP1"
      - "NUP153"
      - "ALDH5A1"
      - "H3C2"
      - "C6orf136"
      - "VARS2"
      - "MSH5"
      - "TNXB"
      - "HLA-DRB5"
      - "HLA-DRB1"
      - "COL11A2"
      - "ITPR3"
      - "SPDEF"
      - "LHFPL5"
      - "PEX6"
      - "TFAP2B"
      - "EYS"
      - "COL12A1"
      - "LOC105377864"
      - "LAMA4"
      - "LAMA2"
      - "ENPP1"
      - "IL20RA"
      - "TNFAIP3"
      - "STX11"
      - "EPM2A"
      - "CCDC170"
      - "SYNE1"
      - "ARID1B"
      - "SOD2"
      - "PRR18"
      - "TBP"
      - "TMEM184A"
      - "CRPPA"
      - "DNAH11"
      - "GARS1"
      - "URGCP"
      - "LOC124901648"
      - "LOC124901651"
      - "AUTS2"
      - "NCF1"
      - "SEMA3A"
      - "MTERF1"
      - "PEX1"
      - "DYNC1I1"
      - "RASA4B"
      - "RELN"
      - "SLC26A4"
      - "FOXP2"
      - "CFTR"
      - "PAX4"
      - "LEP"
      - "BRAF"
      - "MRPS33"
      - "MGAM2"
      - "CLCN1"
      - "ARHGEF34P"
      - "PRKAG2"
      - "EN2"
      - "OR4F21"
      - "CSMD1"
      - "MCPH1"
      - "LOC128966594"
      - "FAM90A19"
      - "GATA4"
      - "CHMP7"
      - "ESCO2"
      - "KCNU1"
      - "FGFR1"
      - "PRKDC"
      - "CHD7"
      - "TTPA"
      - "CYP7B1"
      - "EYA1"
      - "GDAP1"
      - "ZBTB10"
      - "PDP1"
      - "CFAP418"
      - "POP1"
      - "CSMD3"
      - "TRPS1"
      - "TG"
      - "DENND3"
      - "TOP1MT"
      - "PLEC"
      - "WASHC1"
      - "VLDLR"
      - "BRD10"
      - "MPDZ"
      - "SLC24A2"
      - "CDKN2B"
      - "TOPORS"
      - "B4GALT1"
      - "MYORG"
      - "GALT"
      - "RMRP"
      - "GNE"
      - "ZBTB5"
      - "CNTNAP3"
      - "LOC107987067"
      - "SPATA31D1"
      - "TGFBR1"
      - "INVS"
      - "FKTN"
      - "TMEM38B"
      - "SLC31A2"
      - "CDK5RAP2"
      - "LMX1B"
      - "CRAT"
      - "C9orf78"
      - "ADAMTSL2"
      - "VAV2"
      - "NOTCH1"
      - "FBXW5"
      - "NDOR1"
      - "GATA3"
      - "PTF1A"
      - "MYO3A"
      - "RET"
      - "ANKRD30BP3"
      - "AGAP4"
      - "SHLD2P1"
      - "UNC5B"
      - "CDH23"
      - "VCL"
      - "ZMIZ1"
      - "NRG3"
      - "PAPSS2"
      - "PTEN"
      - "ANKRD1"
      - "FFAR4"
      - "TM9SF3"
      - "ENTPD7"
      - "TWNK"
      - "POLL"
      - "CALHM2"
      - "ADRA2A"
      - "INPP5F"
      - "TACC2"
      - "ACADSB"
      - "PTPRE"
      - "PAOX"
      - "ANO9"
      - "MUC6"
      - "MUC2"
      - "INS"
      - "TPP1"
      - "NUCB2"
      - "KCNJ11"
      - "ABCC8"
      - "CSRP3-AS1"
      - "HTATIP2"
      - "ANO5"
      - "PAX6"
      - "WT1"
      - "MADD"
      - "OR8H3"
      - "ZDHHC5"
      - "GLYATL1"
      - "LTBP3"
      - "KLC2"
      - "BBS1"
      - "ACTN3"
      - "SPTBN2"
      - "CABP4"
      - "KCNE3"
      - "CAPN5"
      - "MYO7A"
      - "FZD4"
      - "MMP1"
      - "CASP1"
      - "ALG9"
      - "CEP164"
      - "MFRP"
      - "ROBO3"
      - "CDON"
      - "KCNJ5"
      - "IQSEC3"
      - "VWF"
      - "ATN1"
      - "PEX5"
      - "SLCO1B1"
      - "DNM1L"
      - "MUC19"
      - "PRICKLE1"
      - "VDR"
      - "MMP19"
      - "ERBB3"
      - "PAN2"
      - "ARHGAP9"
      - "MARS1"
      - "GRIP1"
      - "CNOT2"
      - "TMPO"
      - "SLC17A8"
      - "IGF1"
      - "WASHC4"
      - "MMAB"
      - "TBX3"
      - "HNF1A"
      - "LOC105370092"
      - "MUC8"
      - "ANKLE2"
      - "GOLGA3"
      - "BRCA2"
      - "SMAD9"
      - "FREM2"
      - "DHRS12"
      - "SLITRK1"
      - "LOC124903229"
      - "MIR17HG"
      - "LOC105377805"
      - "TEP1"
      - "IPO4"
      - "NUBPL"
      - "FANCM"
      - "VCPKMT"
      - "BMP4"
      - "GCH1"
      - "DACT1"
      - "ADAM21"
      - "DNAL1"
      - "ESRRB"
      - "CEP128"
      - "ATXN3"
      - "DICER1"
      - "HHIPL1"
      - "TDRD9"
      - "AHNAK2"
      - "LOC105370714"
      - "LOC102724737"
      - "MAGEL2"
      - "UBE3A"
      - "GOLGA8R"
      - "OTUD7A"
      - "PLA2G4D"
      - "STARD9"
      - "DUOX2"
      - "TRPM7"
      - "WDR72"
      - "LCTL"
      - "CLN6"
      - "LOC112268145"
      - "MAN2C1"
      - "HYKK"
      - "EFL1"
      - "GOLGA6L10"
      - "ALPK3"
      - "BLM"
      - "UNC45A"
      - "PRC1"
      - "IGF1R"
      - "PGAP6"
      - "CAPN15"
      - "RPUSD1"
      - "TPSAB1"
      - "TPSD1"
      - "HS3ST6"
      - "FLYWCH1"
      - "SLX4"
      - "MGRN1"
      - "GRIN2A"
      - "LOC400499"
      - "ABCC1"
      - "SDR42E2"
      - "COG7"
      - "IL4R"
      - "TBX6"
      - "NPIPB13"
      - "ZNF48"
      - "TRIM72"
      - "ORC6"
      - "NOD2"
      - "MMP2"
      - "BBS2"
      - "TRADD"
      - "CDH1"
      - "CHST6"
      - "FOXF1"
      - "ZNF469"
      - "PIEZO1"
      - "MRM3"
      - "SCIMP"
      - "AIPL1"
      - "PITPNM3"
      - "TP53"
      - "COX10"
      - "FLCN"
      - "MYO15A"
      - "SHMT1"
      - "LGALS9C"
      - "GRAP"
      - "AKAP10"
      - "MAP2K3"
      - "KCNJ18"
      - "RSKR"
      - "FAM222B"
      - "SSH2"
      - "CRLF3"
      - "TBC1D3F"
      - "PIGW"
      - "ACACA"
      - "STAT3"
      - "BRCA1"
      - "SLC4A1"
      - "PNPO"
      - "CALCOCO2"
      - "PDK2"
      - "COL1A1"
      - "BRIP1"
      - "LRRC37A3"
      - "TSEN54"
      - "UNC13D"
      - "ACOX1"
      - "ST6GALNAC1"
      - "LOC124904103"
      - "CARD14"
      - "RNF213"
      - "BAIAP2"
      - "MC2R"
      - "CDH2"
      - "KLHL14"
      - "ATP5F1A"
      - "ATP8B1"
      - "NEDD4L"
      - "LMAN1"
      - "RTTN"
      - "IZUMO4"
      - "KDM4B"
      - "INSR"
      - "FBN3"
      - "CERS4"
      - "TYK2"
      - "ZNF44"
      - "PTGER1"
      - "ADGRE2"
      - "SLC5A5"
      - "HAMP"
      - "CD177"
      - "CBLC"
      - "RTN2"
      - "OPA3"
      - "RASIP1"
      - "ZNF701"
      - "SLC4A11"
      - "HSPA12B"
      - "FERMT1"
      - "SEC23B"
      - "ABHD12"
      - "HNF4A"
      - "MATN4"
      - "OCSTAMP"
      - "PCK1"
      - "DIDO1"
      - "NRIP1"
      - "IFNAR2"
      - "KCNE2"
      - "LOC102723769"
      - "IL17RA"
      - "LOC124905153"
      - "SNAP29"
      - "RIMBP3C"
      - "DDTL"
      - "CHEK2"
      - "NF2"
      - "PLA2G3"
      - "TIMP3"
      - "EP300"
      - "TNFRSF13C"
      - "NAGA"
      - "EFCAB6"
      - "PNPLA3"
      - "ASMT"
      - "GYG2"
      - "ZNF41"
      - "ZXDA"
      - "ZNF711"
      - "XIAP"
      - "SAGE1"
      - "PRRG3"
      - "OPN1LW"
      - "G6PD"
  - regulatoryFeatureFilter: {}
  - frequencyFilter:
      maxFrequency: 2.0
  - pathogenicityFilter:
      keepNonPathogenic: true
  - inheritanceFilter: {}
  - omimPrioritiser: {}
outputOptions:
  outputFormats:
  - "HTML"
  - "TSV_GENE"
  - "TSV_VARIANT"
  - "JSON"
  outputFileName: "P00110_11_Exomiseri_REMM"
  outputDirectory: "/mnt/storage_pool/Genomics/VarXOmics/examples/P00110_11"

Filtering Summary

Filter Report Passed filter Failed filter
Gene priority score
    Genes filtered for minimum HIPHIVE_PRIORITY score of 0.5009999871253967
 4642 14529
Failed previous VCF filters
    Removed variants without PASS or . in VCF FILTER field
 1941592 0
Gene id
    Removed variants in genes: [PERM1, KIF1B, MTHFR, TNFRSF1B, DHRS3, PRAMEF18, NBPF1, DDOST, HSPG2, CRYBG2, FCN3, SMPDL3B, EPB41, GJB3, CDCA8, MPL, MMACHC, PCSK9, HOOK1, GBP1, DPYD, DBT, COL11A1, PTPN22, ANXA9, TUFT1, HRNR, FLG, SPRR2E, TPM3, SPTA1, KCNJ9, PEX19, F5, QSOX1, HMCN1, CDC73, CFH, LAMB3, RD3, PACC1, TATDN3, FLVCR1, RAB3GAP2, ITPKB, MTR, RYR2, FH, NLRP3, EIPR1, ZNF513, SLC3A1, MCFD2, MSH2, NRXN1, PNO1, ANXA4, GGCX, CHST10, IL36RN, GLI2, BIN1, LOC124908048, ZEB2, NEB, TANC1, SCN2A, SCN9A, SCN7A, LRP2, HOXD10, HOXD3, AGPS, TTN, STAT1, CCDC150, NDUFS1, FASTKD2, PLEKHM3, CFAP65, SPEG, OBSL1, COL4A3, CHRNG, UGT1A10, GAL3ST2, ITPR1, CAV3, VHL, RAF1, NUP210, EOMES, ACVR2B, SLC25A38, VIPR1, SLC6A20, ALS2CL, KIF9, LAMB2, DNAH12, FLNB, CLDND1, ZPLD1, CCDC191, ZBTB20, GPR156, PCCB, CPA3, HPS3, IFT80, SLC2A2, MUC4, LOC112268458, LOC124900647, CFAP99, SH3BP2, HTT, WFS1, SORCS2, SH3TC1, DRD5, TLR1, SRD5A3, AMBN, STBD1, ARHGAP24, FAM13A, SNCA, BMPR1B, SLC9B1, EGF, MFSD8, RAB33B, FHIP1A, TLR2, FNIP2, PALLD, AGA, CCT5, DNAH5, TRIO, LIFR, CARD6, ITGA2, ANKRD55, PDE4D, GFM2, PDE8B, VCAN, MEF2C, WDR36, HSD17B4, ALDH7A1, MEGF10, UQCRQ, LECT2, TGFBI, KLHL3, HSPA9, PURA, PCDHB3, DIAPH1, SH3TC2, PDE6A, PDGFRB, SLU7, ATP10B, SH3PXD2B, FGFR4, WRNIP1, F13A1, DSP, DTNBP1, NUP153, ALDH5A1, H3C2, C6orf136, VARS2, MSH5, TNXB, HLA-DRB5, HLA-DRB1, COL11A2, ITPR3, SPDEF, LHFPL5, PEX6, TFAP2B, EYS, COL12A1, LOC105377864, LAMA4, LAMA2, ENPP1, IL20RA, TNFAIP3, STX11, EPM2A, CCDC170, SYNE1, ARID1B, SOD2, PRR18, TBP, TMEM184A, CRPPA, DNAH11, GARS1, URGCP, LOC124901648, LOC124901651, AUTS2, NCF1, SEMA3A, MTERF1, PEX1, DYNC1I1, RASA4B, RELN, SLC26A4, FOXP2, CFTR, PAX4, LEP, BRAF, MRPS33, MGAM2, CLCN1, ARHGEF34P, PRKAG2, EN2, OR4F21, CSMD1, MCPH1, LOC128966594, FAM90A19, GATA4, CHMP7, ESCO2, KCNU1, FGFR1, PRKDC, CHD7, TTPA, CYP7B1, EYA1, GDAP1, ZBTB10, PDP1, CFAP418, POP1, CSMD3, TRPS1, TG, DENND3, TOP1MT, PLEC, WASHC1, VLDLR, BRD10, MPDZ, SLC24A2, CDKN2B, TOPORS, B4GALT1, MYORG, GALT, RMRP, GNE, ZBTB5, CNTNAP3, LOC107987067, SPATA31D1, TGFBR1, INVS, FKTN, TMEM38B, SLC31A2, CDK5RAP2, LMX1B, CRAT, C9orf78, ADAMTSL2, VAV2, NOTCH1, FBXW5, NDOR1, GATA3, PTF1A, MYO3A, RET, ANKRD30BP3, AGAP4, SHLD2P1, UNC5B, CDH23, VCL, ZMIZ1, NRG3, PAPSS2, PTEN, ANKRD1, FFAR4, TM9SF3, ENTPD7, TWNK, POLL, CALHM2, ADRA2A, INPP5F, TACC2, ACADSB, PTPRE, PAOX, ANO9, MUC6, MUC2, INS, TPP1, NUCB2, KCNJ11, ABCC8, CSRP3-AS1, HTATIP2, ANO5, PAX6, WT1, MADD, OR8H3, ZDHHC5, GLYATL1, LTBP3, KLC2, BBS1, ACTN3, SPTBN2, CABP4, KCNE3, CAPN5, MYO7A, FZD4, MMP1, CASP1, ALG9, CEP164, MFRP, ROBO3, CDON, KCNJ5, IQSEC3, VWF, ATN1, PEX5, SLCO1B1, DNM1L, MUC19, PRICKLE1, VDR, MMP19, ERBB3, PAN2, ARHGAP9, MARS1, GRIP1, CNOT2, TMPO, SLC17A8, IGF1, WASHC4, MMAB, TBX3, HNF1A, LOC105370092, MUC8, ANKLE2, GOLGA3, BRCA2, SMAD9, FREM2, DHRS12, SLITRK1, LOC124903229, MIR17HG, LOC105377805, TEP1, IPO4, NUBPL, FANCM, VCPKMT, BMP4, GCH1, DACT1, ADAM21, DNAL1, ESRRB, CEP128, ATXN3, DICER1, HHIPL1, TDRD9, AHNAK2, LOC105370714, LOC102724737, MAGEL2, UBE3A, GOLGA8R, OTUD7A, PLA2G4D, STARD9, DUOX2, TRPM7, WDR72, LCTL, CLN6, LOC112268145, MAN2C1, HYKK, EFL1, GOLGA6L10, ALPK3, BLM, UNC45A, PRC1, IGF1R, PGAP6, CAPN15, RPUSD1, TPSAB1, TPSD1, HS3ST6, FLYWCH1, SLX4, MGRN1, GRIN2A, LOC400499, ABCC1, SDR42E2, COG7, IL4R, TBX6, NPIPB13, ZNF48, TRIM72, ORC6, NOD2, MMP2, BBS2, TRADD, CDH1, CHST6, FOXF1, ZNF469, PIEZO1, MRM3, SCIMP, AIPL1, PITPNM3, TP53, COX10, FLCN, MYO15A, SHMT1, LGALS9C, GRAP, AKAP10, MAP2K3, KCNJ18, RSKR, FAM222B, SSH2, CRLF3, TBC1D3F, PIGW, ACACA, STAT3, BRCA1, SLC4A1, PNPO, CALCOCO2, PDK2, COL1A1, BRIP1, LRRC37A3, TSEN54, UNC13D, ACOX1, ST6GALNAC1, LOC124904103, CARD14, RNF213, BAIAP2, MC2R, CDH2, KLHL14, ATP5F1A, ATP8B1, NEDD4L, LMAN1, RTTN, IZUMO4, KDM4B, INSR, FBN3, CERS4, TYK2, ZNF44, PTGER1, ADGRE2, SLC5A5, HAMP, CD177, CBLC, RTN2, OPA3, RASIP1, ZNF701, SLC4A11, HSPA12B, FERMT1, SEC23B, ABHD12, HNF4A, MATN4, OCSTAMP, PCK1, DIDO1, NRIP1, IFNAR2, KCNE2, LOC102723769, IL17RA, LOC124905153, SNAP29, RIMBP3C, DDTL, CHEK2, NF2, PLA2G3, TIMP3, EP300, TNFRSF13C, NAGA, EFCAB6, PNPLA3, ASMT, GYG2, ZNF41, ZXDA, ZNF711, XIAP, SAGE1, PRRG3, OPN1LW, G6PD]
 152708 1788884
Regulatory feature
    Variants found within a regulatory region or <= 20 Kb upstream of the nearest gene
 41900 110808
Frequency
    Variants filtered for maximum allele frequency of 2.00%
 2544 39356
Pathogenicity
    Retained all non-pathogenic variants of all types. Scoring was applied, but the filter passed all variants.
 2544 0
Inheritance
    Variants filtered for compatibility with AUTOSOMAL_DOMINANT, AUTOSOMAL_RECESSIVE, X_RECESSIVE, X_DOMINANT, MITOCHONDRIAL inheritance.
 2537 7

Variant Type Distribution

Variant Type P00110_BL_DNA_11
FRAMESHIFT_ELONGATION 1
FRAMESHIFT_TRUNCATION 1
FRAMESHIFT_VARIANT 3
INTERNAL_FEATURE_ELONGATION 0
FEATURE_TRUNCATION 0
MNV 0
STOP_GAINED 1
STOP_LOST 0
START_LOST 0
SPLICE_ACCEPTOR_VARIANT 0
SPLICE_DONOR_VARIANT 0
MISSENSE_VARIANT 91
INFRAME_INSERTION 3
DISRUPTIVE_INFRAME_INSERTION 1
INFRAME_DELETION 0
DISRUPTIVE_INFRAME_DELETION 1
FIVE_PRIME_UTR_TRUNCATION 0
THREE_PRIME_UTR_TRUNCATION 0
SPLICE_REGION_VARIANT 8
STOP_RETAINED_VARIANT 0
INITIATOR_CODON_VARIANT 0
SYNONYMOUS_VARIANT 19
CODING_TRANSCRIPT_INTRON_VARIANT 1797
FIVE_PRIME_UTR_EXON_VARIANT 6
THREE_PRIME_UTR_EXON_VARIANT 40
FIVE_PRIME_UTR_INTRON_VARIANT 207
THREE_PRIME_UTR_INTRON_VARIANT 0
NON_CODING_TRANSCRIPT_EXON_VARIANT 0
NON_CODING_TRANSCRIPT_INTRON_VARIANT 0
UPSTREAM_GENE_VARIANT 70
DOWNSTREAM_GENE_VARIANT 52
INTERGENIC_VARIANT 223
REGULATORY_REGION_VARIANT 13

Prioritised Genes

BRCA2

Exomiser Score: 0.998 (p=2.0E-6)

Phenotype Score: 0.998

Variant Score: 1.000

Phenotype matches:
Phenotypic similarity 0.998 to Breast-ovarian cancer, familial, 2 associated with BRCA2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Phenotypic similarity 0.392 to mouse mutant involving BRCA2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002114, abnormal axial skeleton morphology
HP:0006625, Multifocal breast carcinoma - MP:0002114, abnormal axial skeleton morphology
Proximity score 0.515 in interactome to PALB2 and phenotypic similarity 0.998 to Breast-ovarian cancer, familial, susceptibility to, 5 associated with PALB2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.515 in interactome to PALB2 and phenotypic similarity 0.306 to mouse mutant of PALB2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002825, abnormal notochord morphology
HP:0006625, Multifocal breast carcinoma - MP:0002825, abnormal notochord morphology
Known diseases:
OMIM:114480 Breast cancer, male, susceptibility to (susceptibility)
OMIM:155255 Medulloblastoma (susceptibility)
OMIM:176807 Prostate cancer (susceptibility)
OMIM:194070 Wilms tumor - autosomal dominant
OMIM:605724 Fanconi anemia, complementation group D1 - autosomal recessive
OMIM:612555 Breast-ovarian cancer, familial, 2 (susceptibility)
OMIM:613029 Glioblastoma 3 (susceptibility)
OMIM:613347 Pancreatic cancer 2 (susceptibility)
ORPHA:1333 Familial pancreatic carcinoma (susceptibility)
ORPHA:145 Hereditary breast and/or ovarian cancer syndrome - autosomal dominant
ORPHA:654 Nephroblastoma - autosomal dominant
ORPHA:70567 Cholangiocarcinoma (unconfirmed)
ORPHA:84 Fanconi anemia - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.998 (p=2.0E-6)

Phenotype Score: 0.998

Variant Score: 1.000

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.998 to OMIM:612555 Breast-ovarian cancer, familial, 2
Phenotypic similarity 0.998 to OMIM:114480 Breast cancer, male, susceptibility to
Phenotypic similarity 0.998 to ORPHA:1333 Familial pancreatic carcinoma
Phenotypic similarity 0.998 to ORPHA:145 Hereditary breast and/or ovarian cancer syndrome
Variants contributing to score:
FRAMESHIFT_VARIANT INS 13-32338103-G-GA [0/1] rs397507683
Exomiser ACMG: PATHOGENIC [PVS1, PM2_Supporting, PP4, PP5_VeryStrong]
ClinVar: PATHOGENIC (REVIEWED_BY_EXPERT_PANEL)
Variant score: 1.000 CONTRIBUTING VARIANT WHITELIST VARIANT
Transcripts:
BRCA2:ENST00000380152.8:c.3751dup:p.(Thr1251Asnfs*14)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.059 (p=3.1E-1)

Phenotype Score: 0.515

Variant Score: 0.564

No phenotype matches to diseases with this MOI.
Variants contributing to score:
FRAMESHIFT_VARIANT INS 13-32338103-G-GA [0/1] rs397507683
Exomiser ACMG: PATHOGENIC [PVS1, PM2_Supporting, PP5_VeryStrong]
ClinVar: PATHOGENIC (REVIEWED_BY_EXPERT_PANEL)
Variant score: 1.000 CONTRIBUTING VARIANT WHITELIST VARIANT
Transcripts:
BRCA2:ENST00000380152.8:c.3751dup:p.(Thr1251Asnfs*14)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 13-32365109-CTT-C [0/1] rs57551462
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.127 CONTRIBUTING VARIANT
Transcripts:
BRCA2:ENST00000380152.8:c.8331+1577_8331+1578del:p.(=)
Pathogenicity Data:
Best Score: 0.127243
REMM: 0.127
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 13-32368001-CTTTTTTTTTT-C [1/1] rs71071031
Variant score: 0.171
Transcripts:
BRCA2:ENST00000380152.8:c.8332-2400_8332-2391del:p.(=)
Pathogenicity Data:
Best Score: 0.170955
REMM: 0.171
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 13-32343109-G-C [0/1] rs111604929
Variant score: 0.001
Transcripts:
BRCA2:ENST00000380152.8:c.6842-1449G>C:p.(=)
Pathogenicity Data:
Best Score: 0.00115
REMM: 0.001
Frequency Data:
UK10K: 0.4496%
gnomAD_G_AFR: 0.0578%
gnomAD_G_AMR: 0.1244%
gnomAD_G_NFE: 0.3325%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 13-32343436-C-G [0/1] rs11571668
ClinVar: BENIGN (REVIEWED_BY_EXPERT_PANEL)
Variant score: 0.000
Transcripts:
BRCA2:ENST00000380152.8:c.6842-1122C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.1240%
gnomAD_G_AFR: 0.1927%
gnomAD_G_AMR: 1.3042%
gnomAD_G_NFE: 1.0895%
gnomAD_G_SAS: 0.3318%

BRIP1

Exomiser Score: 0.996 (p=2.8E-4)

Phenotype Score: 0.998

Variant Score: 0.917

Phenotype matches:
Phenotypic similarity 0.998 to Hereditary breast and/or ovarian cancer syndrome associated with BRIP1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.514 in interactome to PALB2 and phenotypic similarity 0.998 to Breast-ovarian cancer, familial, susceptibility to, 5 associated with PALB2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.514 in interactome to PALB2 and phenotypic similarity 0.306 to mouse mutant of PALB2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002825, abnormal notochord morphology
HP:0006625, Multifocal breast carcinoma - MP:0002825, abnormal notochord morphology
Known diseases:
OMIM:114480 Breast cancer, early-onset, susceptibility to (susceptibility)
OMIM:609054 Fanconi anemia, complementation group J - autosomal recessive
ORPHA:145 Hereditary breast and/or ovarian cancer syndrome - autosomal dominant
ORPHA:84 Fanconi anemia - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.996 (p=2.8E-4)

Phenotype Score: 0.998

Variant Score: 0.917

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.998 to ORPHA:145 Hereditary breast and/or ovarian cancer syndrome
Phenotypic similarity 0.998 to OMIM:114480 Breast cancer, early-onset, susceptibility to
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-61738549-A-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting, PP4]
Variant score: 0.917 CONTRIBUTING VARIANT
Transcripts:
BRIP1:ENST00000259008.7:c.2379+4464T>G:p.(=)
Pathogenicity Data:
Best Score: 0.917163
REMM: 0.917
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.444 (p=1.1E-1)

Phenotype Score: 0.514

Variant Score: 0.840

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-61738549-A-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.917 CONTRIBUTING VARIANT
Transcripts:
BRIP1:ENST00000259008.7:c.2379+4464T>G:p.(=)
Pathogenicity Data:
Best Score: 0.917163
REMM: 0.917
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 17-61728971-AGGAGGGT-A [0|1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.763 CONTRIBUTING VARIANT
Transcripts:
BRIP1:ENST00000259008.7:c.2380-12915_2380-12909del:p.(=)
Pathogenicity Data:
Best Score: 0.763451
REMM: 0.763
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-61685163-A-G [0/1] rs544948209
Variant score: 0.711
Transcripts:
BRIP1:ENST00000259008.7:c.2905+673T>C:p.(=)
Pathogenicity Data:
Best Score: 0.717037
REMM: 0.717
Frequency Data:
UK10K: 0.0529%
gnomAD_G_AMR: 0.0196%
gnomAD_G_NFE: 0.0456%
gnomAD_G_SAS: 0.0621%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-61732693-A-C [0/1]
Variant score: 0.703
Transcripts:
BRIP1:ENST00000259008.7:c.2379+10320T>G:p.(=)
Pathogenicity Data:
Best Score: 0.702846
REMM: 0.703
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-61791488-C-CAAAAAAAA [0/1]
Variant score: 0.576
Transcripts:
BRIP1:ENST00000259008.7:c.1473+2108_1473+2109insTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.575658
REMM: 0.576
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-61814870-T-A [0/1] rs74623868
Variant score: 0.495
Transcripts:
BRIP1:ENST00000259008.7:c.628-6113A>T:p.(=)
Pathogenicity Data:
Best Score: 0.550067
REMM: 0.550
Frequency Data:
UK10K: 0.3174%
gnomAD_G_AFR: 0.0529%
gnomAD_G_AMR: 0.5502%
gnomAD_G_EAS: 0.0386%
gnomAD_G_NFE: 0.3164%
gnomAD_G_SAS: 0.0208%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 17-61713207-GT-G [0/1] rs548439377
Variant score: 0.473
Transcripts:
BRIP1:ENST00000259008.7:c.2492+2743del:p.(=)
Pathogenicity Data:
Best Score: 0.526898
REMM: 0.527
Frequency Data:
UK10K: 0.2909%
gnomAD_G_AFR: 0.0482%
gnomAD_G_AMR: 0.5623%
gnomAD_G_EAS: 0.0386%
gnomAD_G_NFE: 0.3102%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 17-61836108-CTT-C [0/1] rs71153409
Variant score: 0.414
Transcripts:
BRIP1:ENST00000259008.7:c.627+10991_627+10992del:p.(=)
Pathogenicity Data:
Best Score: 0.414022
REMM: 0.414
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 17-61721692-CT-C [0/1] rs71150632
Variant score: 0.396
Transcripts:
BRIP1:ENST00000259008.7:c.2380-5630del:p.(=)
Pathogenicity Data:
Best Score: 0.39633
REMM: 0.396
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-61826729-A-AG [0/1]
Variant score: 0.210
Transcripts:
BRIP1:ENST00000259008.7:c.628-17973_628-17972insC:p.(=)
Pathogenicity Data:
Best Score: 0.210329
REMM: 0.210
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 17-61836108-CT-C [0/1] rs71153409
Variant score: 0.190
Transcripts:
BRIP1:ENST00000259008.7:c.627+10992del:p.(=)
Pathogenicity Data:
Best Score: 0.190178
REMM: 0.190
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-61826731-T-A [0/1]
Variant score: 0.171
Transcripts:
BRIP1:ENST00000259008.7:c.628-17974A>T:p.(=)
Pathogenicity Data:
Best Score: 0.171081
REMM: 0.171
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 17-61697336-CAAAAAA-C [0/1]
Variant score: 0.127
Transcripts:
BRIP1:ENST00000259008.7:c.2493-3830_2493-3825del:p.(=)
Pathogenicity Data:
Best Score: 0.127119
REMM: 0.127
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 17-61697336-CAAAAAAAAAAAA-C [0/1]
Variant score: 0.127
Transcripts:
BRIP1:ENST00000259008.7:c.2493-3836_2493-3825del:p.(=)
Pathogenicity Data:
Best Score: 0.127119
REMM: 0.127
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-61731645-C-T [0/1] rs537387610
Variant score: 0.093
Transcripts:
BRIP1:ENST00000259008.7:c.2379+11368G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0939377
REMM: 0.094
Frequency Data:
UK10K: 0.0529%
gnomAD_G_AMR: 0.0196%
gnomAD_G_NFE: 0.0470%
gnomAD_G_SAS: 0.0621%
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-61804954-C-CTG [0/1] rs59414906
Variant score: 0.061
Transcripts:
BRIP1:ENST00000259008.7:c.919-3481_919-3480insCA:p.(=)
Pathogenicity Data:
Best Score: 0.110629
REMM: 0.111
Frequency Data:
gnomAD_G_AFR: 0.4566%
gnomAD_G_AMR: 0.7434%
gnomAD_G_EAS: 1.4656%
gnomAD_G_NFE: 0.4438%
gnomAD_G_SAS: 0.7194%
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-61728979-T-TCACCCTC [0|1]
Variant score: 0.001
Transcripts:
BRIP1:ENST00000259008.7:c.2380-12917_2380-12916insGAGGGTG:p.(=)
Pathogenicity Data:
Best Score: 6.0E-4
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-61858434-C-T [0/1] rs565188495
Variant score: 0.000
Transcripts:
BRIP1:ENST00000259008.7:c.206-1203G>A:p.(=)
Pathogenicity Data:
Best Score: 3.33333E-4
REMM: 0.000
Frequency Data:
UK10K: 0.3306%
gnomAD_G_AFR: 0.1304%
gnomAD_G_AMR: 0.3256%
gnomAD_G_EAS: 0.0590%
gnomAD_G_NFE: 0.4449%
gnomAD_G_SAS: 0.1669%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-61823850-C-T [0/1] rs76895044
Variant score: 0.000
Transcripts:
BRIP1:ENST00000259008.7:c.628-15093G>A:p.(=)
Pathogenicity Data:
Best Score: 3.33333E-4
REMM: 0.000
Frequency Data:
UK10K: 0.4232%
gnomAD_G_AFR: 0.0976%
gnomAD_G_AMR: 0.1322%
gnomAD_G_EAS: 0.0198%
gnomAD_G_NFE: 0.5748%
gnomAD_G_SAS: 0.7334%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-61720509-G-A [0/1] rs1013587248
Variant score: 0.000
Transcripts:
BRIP1:ENST00000259008.7:c.2380-4446C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0097%
gnomAD_G_AMR: 0.0066%
gnomAD_G_NFE: 0.0015%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-61748134-G-C [0/1] rs190639775
Variant score: 0.000
Transcripts:
BRIP1:ENST00000259008.7:c.2098-3543C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.3042%
gnomAD_G_AFR: 0.0481%
gnomAD_G_AMR: 0.5491%
gnomAD_G_NFE: 0.3088%
gnomAD_G_SAS: 0.0208%

PALLD

Exomiser Score: 0.995 (p=3.6E-4)

Phenotype Score: 0.998

Variant Score: 0.894

Phenotype matches:
Phenotypic similarity 0.998 to Familial pancreatic carcinoma associated with PALLD.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.500 in interactome to SPTBN1 and phenotypic similarity 0.685 to Developmental delay, impaired speech, and behavioral abnormalities associated with SPTBN1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0032408, Breast mass
HP:0006625, Multifocal breast carcinoma - HP:0032408, Breast mass
Known diseases:
OMIM:606856 Pancreatic cancer, susceptibility to, 1 (susceptibility)
ORPHA:1333 Familial pancreatic carcinoma (susceptibility)
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.995 (p=3.6E-4)

Phenotype Score: 0.998

Variant Score: 0.894

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.998 to ORPHA:1333 Familial pancreatic carcinoma
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168612837-A-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting, PP4]
Variant score: 0.894 CONTRIBUTING VARIANT
Transcripts:
PALLD:ENST00000505667.6:c.909-55353A>C:p.(=)
Pathogenicity Data:
Best Score: 0.89415
REMM: 0.894
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.048 (p=3.3E-1)

Phenotype Score: 0.250

Variant Score: 0.839

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168612837-A-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.894 CONTRIBUTING VARIANT
Transcripts:
PALLD:ENST00000505667.6:c.909-55353A>C:p.(=)
Pathogenicity Data:
Best Score: 0.89415
REMM: 0.894
Frequency Data:
No frequency data
SPLICE_REGION_VARIANT SNV 4-168894685-G-A [0/1] rs200060953
Exomiser ACMG: LIKELY_BENIGN [BP6_Strong]
ClinVar: BENIGN_OR_LIKELY_BENIGN (CRITERIA_PROVIDED_MULTIPLE_SUBMITTERS_NO_CONFLICTS)
Variant score: 0.783 CONTRIBUTING VARIANT
Transcripts:
PALLD:ENST00000505667.6:c.2199+8G>A:p.?
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.0529%
gnomAD_E_AFR: 0.1467%
gnomAD_E_AMR: 0.0940%
gnomAD_E_NFE: 0.0733%
gnomAD_E_SAS: 0.0826%
gnomAD_G_AFR: 0.0577%
gnomAD_G_AMR: 0.0588%
gnomAD_G_NFE: 0.0926%
gnomAD_G_SAS: 0.1037%
Other passed variants:
UPSTREAM_GENE_VARIANT SNV 4-168493488-T-C [0/1] rs1369028430
Variant score: 0.746
Transcripts:
PALLD:ENST00000505667.6::
Pathogenicity Data:
Best Score: 0.745899
REMM: 0.746
Frequency Data:
gnomAD_G_AFR: 0.0024%
CODING_TRANSCRIPT_INTRON_VARIANT INS 4-168725522-C-CT [0/1] rs1210834634
Variant score: 0.702
Transcripts:
PALLD:ENST00000505667.6:c.1964+13599_1964+13600insT:p.(=)
Pathogenicity Data:
Best Score: 0.70156
REMM: 0.702
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-168507543-G-A [0/1]
Variant score: 0.670
Transcripts:
PALLD:ENST00000505667.6:c.-82-3880G>A:p.(=)
Pathogenicity Data:
Best Score: 0.669952
REMM: 0.670
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 4-168680481-CA-C [0/1]
Variant score: 0.663
Transcripts:
PALLD:ENST00000505667.6:c.1088-850del:p.(=)
Pathogenicity Data:
Best Score: 0.663078
REMM: 0.663
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 4-168647780-CA-C [0/1]
Variant score: 0.657
Transcripts:
PALLD:ENST00000505667.6:c.909-20409del:p.(=)
Pathogenicity Data:
Best Score: 0.656639
REMM: 0.657
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 4-168642285-A-AT [0/1]
Variant score: 0.638
Transcripts:
PALLD:ENST00000505667.6:c.909-25905_909-25904insT:p.(=)
Pathogenicity Data:
Best Score: 0.638381
REMM: 0.638
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168845624-T-C [0/1] rs115491569
Variant score: 0.626
Transcripts:
PALLD:ENST00000505667.6:c.1965-45298T>C:p.(=)
Pathogenicity Data:
Best Score: 0.908351
REMM: 0.908
Frequency Data:
UK10K: 0.4099%
gnomAD_G_AFR: 1.1937%
gnomAD_G_AMR: 0.4446%
gnomAD_G_NFE: 0.6498%
gnomAD_G_SAS: 0.1658%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168804848-G-A [0/1] rs569551396
Variant score: 0.605
Transcripts:
PALLD:ENST00000505667.6:c.1965-86074G>A:p.(=)
Pathogenicity Data:
Best Score: 0.607142
REMM: 0.607
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0262%
gnomAD_G_NFE: 0.0235%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168671946-T-G [0/1] rs879359812
Variant score: 0.559
Transcripts:
PALLD:ENST00000505667.6:c.1087+3578T>G:p.(=)
Pathogenicity Data:
Best Score: 0.562287
REMM: 0.562
Frequency Data:
gnomAD_G_AMR: 0.0131%
gnomAD_G_EAS: 0.0384%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 4-168905790-CT-C [1/1] rs59427697
Variant score: 0.517
Transcripts:
PALLD:ENST00000505667.6:c.2622+1885del:p.(=)
Pathogenicity Data:
Best Score: 0.517315
REMM: 0.517
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168721287-C-T [0/1] rs143922343
Variant score: 0.517
Transcripts:
PALLD:ENST00000505667.6:c.1964+9364C>T:p.(=)
Pathogenicity Data:
Best Score: 0.545359
REMM: 0.545
Frequency Data:
UK10K: 0.2513%
gnomAD_G_AFR: 0.0530%
gnomAD_G_AMR: 0.1897%
gnomAD_G_NFE: 0.3236%
gnomAD_G_SAS: 0.2285%
CODING_TRANSCRIPT_INTRON_VARIANT INS 4-168785846-G-GATATATATATATATAT [0/1]
Variant score: 0.495
Transcripts:
PALLD:ENST00000505667.6:c.1964+73923_1964+73924insATATATATATATATAT:p.(=)
Pathogenicity Data:
Best Score: 0.494639
REMM: 0.495
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 4-168922102-TACACACACACACAC-T [1/1] rs35503011
Variant score: 0.406
Transcripts:
PALLD:ENST00000505667.6:c.3058+362_3058+375del:p.(=)
Pathogenicity Data:
Best Score: 0.406249
REMM: 0.406
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 4-168590864-GT-G [0/1] rs371992201
Variant score: 0.345
Transcripts:
PALLD:ENST00000505667.6:c.909-77325del:p.(=)
Pathogenicity Data:
Best Score: 0.34522
REMM: 0.345
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 4-168590864-GTTTTT-G [0/1] rs371992201
Variant score: 0.345
Transcripts:
PALLD:ENST00000505667.6:c.909-77325_909-77321del:p.(=)
Pathogenicity Data:
Best Score: 0.34522
REMM: 0.345
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 4-168709624-G-GGGGAA [0/1]
Variant score: 0.329
Transcripts:
PALLD:ENST00000505667.6:c.1621+477_1621+478insGGGAA:p.(=)
Pathogenicity Data:
Best Score: 0.329221
REMM: 0.329
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 4-168709628-G-GGGGAA [0/1]
Variant score: 0.327
Transcripts:
PALLD:ENST00000505667.6:c.1621+481_1621+482insGGGAA:p.(=)
Pathogenicity Data:
Best Score: 0.326808
REMM: 0.327
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 4-168709629-A-AGTG [0/1]
Variant score: 0.327
Transcripts:
PALLD:ENST00000505667.6:c.1621+482_1621+483insGTG:p.(=)
Pathogenicity Data:
Best Score: 0.326808
REMM: 0.327
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168709630-A-G [0/1] rs78679792
Variant score: 0.327
Transcripts:
PALLD:ENST00000505667.6:c.1621+483A>G:p.(=)
Pathogenicity Data:
Best Score: 0.326808
REMM: 0.327
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 4-168709612-GA-G [1/1] rs1454630208
Variant score: 0.294
Transcripts:
PALLD:ENST00000505667.6:c.1621+466del:p.(=)
Pathogenicity Data:
Best Score: 0.293892
REMM: 0.294
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 4-168709633-A-AGTGGGGG [0/1]
Variant score: 0.268
Transcripts:
PALLD:ENST00000505667.6:c.1621+486_1621+487insGTGGGGG:p.(=)
Pathogenicity Data:
Best Score: 0.268012
REMM: 0.268
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 4-168934299-AAAAAAG-A [0/1]
Variant score: 0.259
Transcripts:
PALLD:ENST00000505667.6::
Pathogenicity Data:
Best Score: 0.258846
REMM: 0.259
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 4-168774727-C-CAAAAAAAAA [0/1]
Variant score: 0.251
Transcripts:
PALLD:ENST00000505667.6:c.1964+62804_1964+62805insAAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.250851
REMM: 0.251
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 4-168887116-C-CA [1/1]
Variant score: 0.241
Transcripts:
PALLD:ENST00000505667.6:c.1965-3806_1965-3805insA:p.(=)
Pathogenicity Data:
Best Score: 0.241352
REMM: 0.241
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 4-168713942-GT-G [0/1] rs34942776
Variant score: 0.238
Transcripts:
PALLD:ENST00000505667.6:c.1964+2020del:p.(=)
Pathogenicity Data:
Best Score: 0.238004
REMM: 0.238
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168793361-G-A [1|1] rs34609466
Variant score: 0.223
Transcripts:
PALLD:ENST00000505667.6:c.1964+81438G>A:p.(=)
Pathogenicity Data:
Best Score: 0.245392
REMM: 0.245
Frequency Data:
gnomAD_G_AFR: 0.1269%
gnomAD_G_AMR: 0.3103%
gnomAD_G_EAS: 0.0547%
gnomAD_G_NFE: 0.5220%
gnomAD_G_SAS: 0.3347%
INTERGENIC_VARIANT DEL 4-168934281-AC-A [0/1]
Variant score: 0.154
Transcripts:
PALLD:ENST00000505667.6::
Pathogenicity Data:
Best Score: 0.154411
REMM: 0.154
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168872178-A-C [0/1] rs1054884477
Variant score: 0.105
Transcripts:
PALLD:ENST00000505667.6:c.1965-18744A>C:p.(=)
Pathogenicity Data:
Best Score: 0.105494
REMM: 0.105
Frequency Data:
gnomAD_G_EAS: 0.0578%
gnomAD_G_NFE: 0.0015%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168670664-C-T [0/1] rs1350939708
Variant score: 0.092
Transcripts:
PALLD:ENST00000505667.6:c.1087+2296C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0924052
REMM: 0.092
Frequency Data:
gnomAD_G_AMR: 0.0139%
gnomAD_G_EAS: 0.0611%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 4-168704664-CA-C [1/1]
Variant score: 0.088
Transcripts:
PALLD:ENST00000505667.6:c.1502-4363del:p.(=)
Pathogenicity Data:
Best Score: 0.0878825
REMM: 0.088
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 4-168649246-G-GT [0/1] rs377606377
Variant score: 0.062
Transcripts:
PALLD:ENST00000505667.6:c.909-18944_909-18943insT:p.(=)
Pathogenicity Data:
Best Score: 0.0638532
REMM: 0.064
Frequency Data:
gnomAD_G_AFR: 0.1829%
gnomAD_G_AMR: 0.0458%
gnomAD_G_EAS: 0.0386%
gnomAD_G_NFE: 0.0176%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 4-168759203-AT-A [1|1]
Variant score: 0.053
Transcripts:
PALLD:ENST00000505667.6:c.1964+47281del:p.(=)
Pathogenicity Data:
Best Score: 0.0533536
REMM: 0.053
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168709584-A-G [1/1] rs1292283984
Variant score: 0.036
Transcripts:
PALLD:ENST00000505667.6:c.1621+437A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0355333
REMM: 0.036
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168709580-A-G [1/1]
Variant score: 0.033
Transcripts:
PALLD:ENST00000505667.6:c.1621+433A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0332
REMM: 0.033
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168709572-A-G [1/1] rs1404875295
Variant score: 0.029
Transcripts:
PALLD:ENST00000505667.6:c.1621+425A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0290667
REMM: 0.029
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 4-168490129-AT-A [0/1] rs35337200
Variant score: 0.028
Transcripts:
PALLD:ENST00000505667.6::
Pathogenicity Data:
Best Score: 0.0279738
REMM: 0.028
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168709617-A-G [0/1]
Variant score: 0.027
Transcripts:
PALLD:ENST00000505667.6:c.1621+470A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0273917
REMM: 0.027
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168709568-A-G [1/1]
Variant score: 0.025
Transcripts:
PALLD:ENST00000505667.6:c.1621+421A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0252536
REMM: 0.025
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168736056-C-T [0/1] rs1290113940
Variant score: 0.013
Transcripts:
PALLD:ENST00000505667.6:c.1964+24133C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0129786
REMM: 0.013
Frequency Data:
gnomAD_G_EAS: 0.0385%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168738653-T-A [0/1] rs6553060
Variant score: 0.011
Transcripts:
PALLD:ENST00000505667.6:c.1964+26730T>A:p.(=)
Pathogenicity Data:
Best Score: 0.0114952
REMM: 0.011
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168709588-A-G [1/1] rs868500486
Variant score: 0.011
Transcripts:
PALLD:ENST00000505667.6:c.1621+441A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0112833
REMM: 0.011
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 4-168489027-G-A [0/1] rs185077057
Variant score: 0.011
Transcripts:
PALLD:ENST00000505667.6::
Pathogenicity Data:
Best Score: 0.0130762
REMM: 0.013
Frequency Data:
gnomAD_G_AFR: 0.0024%
gnomAD_G_EAS: 0.8863%
gnomAD_G_NFE: 0.0029%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168709576-A-G [1/1] rs9799384
Variant score: 0.009
Transcripts:
PALLD:ENST00000505667.6:c.1621+429A>G:p.(=)
Pathogenicity Data:
Best Score: 0.00910833
REMM: 0.009
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168738674-G-A [0/1] rs6849512
Variant score: 0.007
Transcripts:
PALLD:ENST00000505667.6:c.1964+26751G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00694524
REMM: 0.007
Frequency Data:
No frequency data
THREE_PRIME_UTR_EXON_VARIANT SNV 4-168927972-T-A [0/1] rs186567215
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.003
Transcripts:
PALLD:ENST00000505667.6:c.*1792T>A:p.(=)
Pathogenicity Data:
Best Score: 0.00264444
REMM: 0.003
Frequency Data:
gnomAD_E_AFR: 0.1670%
gnomAD_E_NFE: 0.1608%
gnomAD_G_AFR: 0.0505%
gnomAD_G_AMR: 0.0588%
gnomAD_G_NFE: 0.0985%
gnomAD_G_SAS: 0.1036%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168764820-G-A [0/1] rs184596416
Variant score: 0.001
Transcripts:
PALLD:ENST00000505667.6:c.1964+52897G>A:p.(=)
Pathogenicity Data:
Best Score: 9.0E-4
REMM: 0.001
Frequency Data:
gnomAD_G_AMR: 0.0065%
gnomAD_G_EAS: 0.3283%
gnomAD_G_NFE: 0.0029%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168708910-G-A [0/1] rs186259847
Variant score: 0.000
Transcripts:
PALLD:ENST00000505667.6:c.1502-118G>A:p.(=)
Pathogenicity Data:
Best Score: 1.11111E-4
REMM: 0.000
Frequency Data:
UK10K: 0.2645%
gnomAD_E_AFR: 0.0852%
gnomAD_E_AMR: 0.1445%
gnomAD_E_NFE: 0.2955%
gnomAD_E_SAS: 0.3677%
gnomAD_G_AFR: 0.0529%
gnomAD_G_AMR: 0.1505%
gnomAD_G_NFE: 0.3043%
gnomAD_G_SAS: 0.2902%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168709560-A-G [0/1]
Variant score: 0.000
Transcripts:
PALLD:ENST00000505667.6:c.1621+413A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168709564-A-G [1/1] rs374757153
Variant score: 0.000
Transcripts:
PALLD:ENST00000505667.6:c.1621+417A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168762474-A-C [0/1] rs543649270
Variant score: 0.000
Transcripts:
PALLD:ENST00000505667.6:c.1964+50551A>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0121%
gnomAD_G_AMR: 0.0132%
gnomAD_G_EAS: 0.0580%
gnomAD_G_NFE: 0.0103%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168773389-C-A [0/1] rs906321136
Variant score: 0.000
Transcripts:
PALLD:ENST00000505667.6:c.1964+61466C>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AMR: 0.0065%
gnomAD_G_NFE: 0.0088%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-168835729-C-T [0/1] rs181054230
Variant score: 0.000
Transcripts:
PALLD:ENST00000505667.6:c.1965-55193C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.0529%
gnomAD_G_AFR: 1.6594%
gnomAD_G_AMR: 0.2756%
gnomAD_G_NFE: 0.1075%
gnomAD_G_SAS: 0.1460%

BLM

Exomiser Score: 0.987 (p=8.4E-4)

Phenotype Score: 0.950

Variant Score: 0.845

Phenotype matches:
Phenotypic similarity 0.950 to Bloom syndrome associated with BLM.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0100013, Neoplasm of the breast
HP:0006625, Multifocal breast carcinoma - HP:0100013, Neoplasm of the breast
Phenotypic similarity 0.258 to mouse mutant involving BLM.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002416, abnormal proerythroblast morphology
HP:0006625, Multifocal breast carcinoma - MP:0002416, abnormal proerythroblast morphology
Proximity score 0.515 in interactome to RAD54L and phenotypic similarity 0.998 to Breast cancer, invasive ductal associated with RAD54L.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Known diseases:
OMIM:210900 Bloom syndrome - autosomal recessive
ORPHA:125 Bloom syndrome - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.987 (p=8.4E-4)

Phenotype Score: 0.950

Variant Score: 0.845

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.950 to ORPHA:125 Bloom syndrome
Variants contributing to score:
DOWNSTREAM_GENE_VARIANT DEL 15-90819208-TGGTTCCACGGCCCCACAGAGGGTTCGGTGACGCCTGGGAAGGTGCCG-T [1|0] rs1567070294
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PP4]
Variant score: 0.872 CONTRIBUTING VARIANT
Transcripts:
BLM:ENST00000355112.8::
Pathogenicity Data:
Best Score: 0.885674
REMM: 0.886
Frequency Data:
gnomAD_G_AFR: 0.0121%
gnomAD_G_AMR: 0.0396%
gnomAD_G_NFE: 0.0682%
gnomAD_G_SAS: 0.1043%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 15-90787036-CTT-C [0/1] rs11366266
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting, PP4]
Variant score: 0.817 CONTRIBUTING VARIANT
Transcripts:
BLM:ENST00000355112.8:c.2823+1956_2823+1957del:p.(=)
Pathogenicity Data:
Best Score: 0.816976
REMM: 0.817
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.043 (p=3.4E-1)

Phenotype Score: 0.257

Variant Score: 0.817

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 15-90787036-CTT-C [0/1] rs11366266
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.817 CONTRIBUTING VARIANT
Transcripts:
BLM:ENST00000355112.8:c.2823+1956_2823+1957del:p.(=)
Pathogenicity Data:
Best Score: 0.816976
REMM: 0.817
Frequency Data:
No frequency data
Other passed variants:
DOWNSTREAM_GENE_VARIANT SNV 15-90820276-T-C [0/1] rs953040592
Variant score: 0.795
Transcripts:
BLM:ENST00000355112.8::
Pathogenicity Data:
Best Score: 0.79492
REMM: 0.795
Frequency Data:
gnomAD_G_NFE: 0.0015%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 15-90811817-C-A [0/1] rs937378303
Variant score: 0.640
Transcripts:
BLM:ENST00000355112.8:c.4076+411C>A:p.(=)
Pathogenicity Data:
Best Score: 0.64024
REMM: 0.640
Frequency Data:
gnomAD_G_NFE: 0.0015%
INTERGENIC_VARIANT DEL 15-90827247-TGGG-T [0/1] rs537261301
Variant score: 0.588
Transcripts:
BLM:ENST00000355112.8::
Pathogenicity Data:
Best Score: 0.61616
REMM: 0.616
Frequency Data:
UK10K: 0.1719%
gnomAD_G_AFR: 0.0289%
gnomAD_G_AMR: 0.2942%
gnomAD_G_NFE: 0.2559%
gnomAD_G_SAS: 0.1038%
MISSENSE_VARIANT SNV 15-90765340-C-T [0/1] rs146077918
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:2, LB:11, B:2)
Variant score: 0.573
Transcripts:
BLM:ENST00000355112.8:c.2119C>T:p.(Pro707Ser)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.2248%
gnomAD_E_AFR: 0.0448%
gnomAD_E_AMR: 0.1789%
gnomAD_E_EAS: 0.0025%
gnomAD_E_NFE: 0.2281%
gnomAD_E_SAS: 0.1623%
gnomAD_G_AFR: 0.0289%
gnomAD_G_AMR: 0.2876%
gnomAD_G_NFE: 0.2646%
gnomAD_G_SAS: 0.1037%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 15-90789987-GTTTTTTT-G [0/1] rs61059865
Variant score: 0.567
Transcripts:
BLM:ENST00000355112.8:c.2824-661_2824-655del:p.(=)
Pathogenicity Data:
Best Score: 0.566772
REMM: 0.567
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 15-90774066-CT-C [0/1] rs61323062
Variant score: 0.304
Transcripts:
BLM:ENST00000355112.8:c.2555+4481del:p.(=)
Pathogenicity Data:
Best Score: 0.304246
REMM: 0.304
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 15-90699667-CA-C [0/1] rs879400073
Variant score: 0.272
Transcripts:
BLM:ENST00000355112.8::
Pathogenicity Data:
Best Score: 0.279421
REMM: 0.279
Frequency Data:
gnomAD_G_AFR: 0.0533%
gnomAD_G_AMR: 0.1102%
gnomAD_G_NFE: 0.1682%
gnomAD_G_SAS: 0.0231%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 15-90797414-CAAAA-C [0/1]
Variant score: 0.032
Transcripts:
BLM:ENST00000355112.8:c.3211-775_3211-772del:p.(=)
Pathogenicity Data:
Best Score: 0.0323532
REMM: 0.032
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 15-90791538-C-T [0/1] rs183754780
Variant score: 0.000
Transcripts:
BLM:ENST00000355112.8:c.3019+694C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.2380%
gnomAD_G_AFR: 0.0289%
gnomAD_G_AMR: 0.2881%
gnomAD_G_NFE: 0.2632%
gnomAD_G_SAS: 0.1038%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 15-90815036-T-G [0/1] rs567859817
Variant score: 0.000
Transcripts:
BLM:ENST00000355112.8:c.4077-66T>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_E_AFR: 0.0515%
gnomAD_E_AMR: 0.1929%
gnomAD_E_EAS: 0.0027%
gnomAD_E_NFE: 0.2693%
gnomAD_E_SAS: 0.1782%
gnomAD_G_AFR: 0.0481%
gnomAD_G_AMR: 0.6318%
gnomAD_G_NFE: 0.4322%
gnomAD_G_SAS: 0.1759%

SEC23B

Exomiser Score: 0.978 (p=1.1E-3)

Phenotype Score: 0.990

Variant Score: 0.741

Phenotype matches:
Phenotypic similarity 0.990 to ?Cowden syndrome 7 associated with SEC23B.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Phenotypic similarity 0.245 to zebrafish mutant involving SEC23B.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0000916, ventral mandibular arch decreased size, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0000916, ventral mandibular arch decreased size, abnormal
Proximity score 0.509 in interactome to MGAT2 and phenotypic similarity 0.617 to MGAT2-CDG associated with MGAT2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Proximity score 0.509 in interactome to MGAT2 and phenotypic similarity 0.347 to mouse mutant of MGAT2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000069, kyphoscoliosis
HP:0006625, Multifocal breast carcinoma - MP:0000069, kyphoscoliosis
Known diseases:
OMIM:224100 Dyserythropoietic anemia, congenital, type II - autosomal recessive
OMIM:616858 ?Cowden syndrome 7 (unconfirmed)
ORPHA:201 Cowden syndrome - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.978 (p=1.1E-3)

Phenotype Score: 0.990

Variant Score: 0.741

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.990 to OMIM:616858 ?Cowden syndrome 7
Phenotypic similarity 0.904 to ORPHA:201 Cowden syndrome
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 20-18546238-G-C [0/1] rs949378307
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PP4]
Variant score: 0.741 CONTRIBUTING VARIANT
Transcripts:
SEC23B:ENST00000650089.1:c.1743+205G>C:p.(=)
Pathogenicity Data:
Best Score: 0.74239
REMM: 0.742
Frequency Data:
gnomAD_G_NFE: 0.0118%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.034 (p=3.6E-1)

Phenotype Score: 0.509

Variant Score: 0.507

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 20-18546238-G-C [0/1] rs949378307
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.741 CONTRIBUTING VARIANT
Transcripts:
SEC23B:ENST00000650089.1:c.1743+205G>C:p.(=)
Pathogenicity Data:
Best Score: 0.74239
REMM: 0.742
Frequency Data:
gnomAD_G_NFE: 0.0118%
MISSENSE_VARIANT SNV 20-18525868-C-T [0/1] rs146917730
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:1, LB:1, B:4)
Variant score: 0.273 CONTRIBUTING VARIANT
Transcripts:
SEC23B:ENST00000650089.1:c.770C>T:p.(Thr257Ile)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 1.5737%
gnomAD_E_AFR: 0.1912%
gnomAD_E_AMR: 0.4248%
gnomAD_E_EAS: 0.0151%
gnomAD_E_NFE: 1.5505%
gnomAD_E_SAS: 1.4746%
gnomAD_G_AFR: 0.2743%
gnomAD_G_AMR: 0.4118%
gnomAD_G_EAS: 0.0578%
gnomAD_G_NFE: 1.6143%
gnomAD_G_SAS: 1.2852%
Other passed variants:
DOWNSTREAM_GENE_VARIANT DEL 20-18565372-CTT-C [1/1] rs71194251
Variant score: 0.165
Transcripts:
SEC23B:ENST00000650089.1::
Pathogenicity Data:
Best Score: 0.164852
REMM: 0.165
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 20-18557745-CT-C [1/1] rs11477198
Variant score: 0.095
Transcripts:
SEC23B:ENST00000650089.1:c.2214+2573del:p.(=)
Pathogenicity Data:
Best Score: 0.0954024
REMM: 0.095
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 20-18520500-G-A [0/1] rs934638008
Variant score: 0.035
Transcripts:
SEC23B:ENST00000650089.1:c.367-3933G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0348992
REMM: 0.035
Frequency Data:
gnomAD_G_AFR: 0.0048%
gnomAD_G_NFE: 0.0279%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 20-18512912-G-A [0/1] rs118107265
Variant score: 0.001
Transcripts:
SEC23B:ENST00000650089.1:c.279+630G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00156944
REMM: 0.002
Frequency Data:
UK10K: 1.5737%
gnomAD_G_AFR: 0.3905%
gnomAD_G_AMR: 0.4450%
gnomAD_G_EAS: 0.0579%
gnomAD_G_NFE: 1.6219%
gnomAD_G_SAS: 1.2692%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 20-18523321-C-T [0/1]
Variant score: 0.000
Transcripts:
SEC23B:ENST00000650089.1:c.367-1112C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data

BRCA1

Exomiser Score: 0.947 (p=1.6E-3)

Phenotype Score: 0.998

Variant Score: 0.631

Phenotype matches:
Phenotypic similarity 0.998 to Fanconi anemia, complementation group S associated with BRCA1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.515 in interactome to PALB2 and phenotypic similarity 0.998 to Breast-ovarian cancer, familial, susceptibility to, 5 associated with PALB2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.515 in interactome to PALB2 and phenotypic similarity 0.306 to mouse mutant of PALB2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002825, abnormal notochord morphology
HP:0006625, Multifocal breast carcinoma - MP:0002825, abnormal notochord morphology
Known diseases:
OMIM:604370 Breast-ovarian cancer, familial, 1 (susceptibility)
OMIM:617883 Fanconi anemia, complementation group S - autosomal recessive
ORPHA:1333 Familial pancreatic carcinoma (susceptibility)
ORPHA:145 Hereditary breast and/or ovarian cancer syndrome - autosomal dominant
ORPHA:70567 Cholangiocarcinoma (unconfirmed)
ORPHA:84 Fanconi anemia - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.947 (p=1.6E-3)

Phenotype Score: 0.998

Variant Score: 0.631

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.998 to OMIM:617883 Fanconi anemia, complementation group S
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 17-43064827-AT-A [1/1] rs60879064
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting, PP4]
Variant score: 0.631 CONTRIBUTING VARIANT
Transcripts:
BRCA1:ENST00000357654.9:c.5075-877del:p.(=)
Pathogenicity Data:
Best Score: 0.630993
REMM: 0.631
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-43121683-C-CAAA [1/1]
Variant score: 0.367
Transcripts:
BRCA1:ENST00000357654.9:c.80+2333_80+2334insTTT:p.(=)
Pathogenicity Data:
Best Score: 0.366503
REMM: 0.367
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-43096887-G-A [1/1] rs8176146
ClinVar: BENIGN (REVIEWED_BY_EXPERT_PANEL)
Variant score: 0.219
Transcripts:
BRCA1:ENST00000357654.9:c.593+357C>T:p.(=)
Pathogenicity Data:
Best Score: 0.630823
REMM: 0.631
Frequency Data:
UK10K: 1.0579%
gnomAD_G_AFR: 0.2003%
gnomAD_G_AMR: 1.2334%
gnomAD_G_EAS: 0.0386%
gnomAD_G_NFE: 1.2826%
gnomAD_G_SAS: 1.7620%
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-43096376-C-CAAAAAAAAAA [1/1]
Variant score: 0.101
Transcripts:
BRCA1:ENST00000357654.9:c.594-455_594-454insTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.101418
REMM: 0.101
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-43102357-C-CTTTTTTTT [1/1] rs35584960
Variant score: 0.098
Transcripts:
BRCA1:ENST00000357654.9:c.441+1764_441+1765insAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.0983444
REMM: 0.098
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-43087963-T-C [1/1] rs8176167
ClinVar: BENIGN (REVIEWED_BY_EXPERT_PANEL)
Variant score: 0.000
Transcripts:
BRCA1:ENST00000357654.9:c.4185+2981A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.0447%
gnomAD_G_AFR: 0.1977%
gnomAD_G_AMR: 1.2313%
gnomAD_G_EAS: 0.0388%
gnomAD_G_NFE: 1.2842%
gnomAD_G_SAS: 1.7442%

MSH2

Exomiser Score: 0.930 (p=1.8E-3)

Phenotype Score: 0.998

Variant Score: 0.599

Phenotype matches:
Phenotypic similarity 0.998 to Lynch syndrome associated with MSH2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Phenotypic similarity 0.290 to mouse mutant involving MSH2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0003789, increased osteosarcoma incidence
HP:0006625, Multifocal breast carcinoma - MP:0003789, increased osteosarcoma incidence
Proximity score 0.513 in interactome to MGMT and phenotypic similarity 0.950 to Familial melanoma associated with MGMT.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0100013, Neoplasm of the breast
HP:0006625, Multifocal breast carcinoma - HP:0100013, Neoplasm of the breast
Known diseases:
OMIM:120435 Lynch syndrome 1 - autosomal dominant
OMIM:158320 Muir-Torre syndrome - autosomal dominant
OMIM:619096 Mismatch repair cancer syndrome 2 - autosomal recessive
ORPHA:144 Lynch syndrome - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.930 (p=1.8E-3)

Phenotype Score: 0.998

Variant Score: 0.599

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.998 to ORPHA:144 Lynch syndrome
Phenotypic similarity 0.998 to OMIM:158320 Muir-Torre syndrome
Variants contributing to score:
MISSENSE_VARIANT SNV 2-47475039-A-G [0/1] rs371614039
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PP4]
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:12, LB:2, B:1)
Variant score: 0.599 CONTRIBUTING VARIANT
Transcripts:
MSH2:ENST00000233146.7:c.1774A>G:p.(Met592Val)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AMR: 0.0022%
gnomAD_E_NFE: 0.0107%
gnomAD_G_NFE: 0.0118%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.058 (p=3.1E-1)

Phenotype Score: 0.513

Variant Score: 0.563

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 2-47475039-A-G [0/1] rs371614039
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:12, LB:2, B:1)
Variant score: 0.599 CONTRIBUTING VARIANT
Transcripts:
MSH2:ENST00000233146.7:c.1774A>G:p.(Met592Val)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AMR: 0.0022%
gnomAD_E_NFE: 0.0107%
gnomAD_G_NFE: 0.0118%
INTERGENIC_VARIANT DEL 2-47490294-CTT-C [0/1] rs55933603
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.526 CONTRIBUTING VARIANT
Transcripts:
MSH2:ENST00000233146.7::
Pathogenicity Data:
Best Score: 0.526106
REMM: 0.526
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-47436051-C-A [0/1]
Variant score: 0.454
Transcripts:
MSH2:ENST00000233146.7:c.1276+6110C>A:p.(=)
Pathogenicity Data:
Best Score: 0.453645
REMM: 0.454
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 2-47473725-CAAA-C [0/1]
Variant score: 0.453
Transcripts:
MSH2:ENST00000233146.7:c.1760-1299_1760-1297del:p.(=)
Pathogenicity Data:
Best Score: 0.452815
REMM: 0.453
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 2-47447165-CTTTTTTTT-C [0/1] rs34512683
Variant score: 0.447
Transcripts:
MSH2:ENST00000233146.7:c.1386+1509_1386+1516del:p.(=)
Pathogenicity Data:
Best Score: 0.447146
REMM: 0.447
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 2-47498737-C-A [0/1]
Variant score: 0.429
Transcripts:
MSH2:ENST00000233146.7::
Pathogenicity Data:
Best Score: 0.429106
REMM: 0.429
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 2-47413548-GT-G [0/1]
Variant score: 0.390
Transcripts:
MSH2:ENST00000233146.7:c.793-720del:p.(=)
Pathogenicity Data:
Best Score: 0.389762
REMM: 0.390
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-47406788-A-G [0/1]
Variant score: 0.328
Transcripts:
MSH2:ENST00000233146.7:c.212-1613A>G:p.(=)
Pathogenicity Data:
Best Score: 0.328228
REMM: 0.328
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 2-47415456-A-ATTT [0/1] rs763081323
Variant score: 0.311
Transcripts:
MSH2:ENST00000233146.7:c.943-840_943-839insTTT:p.(=)
Pathogenicity Data:
Best Score: 0.311269
REMM: 0.311
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 2-47491082-GTT-G [0/1] rs869194469
Variant score: 0.300
Transcripts:
MSH2:ENST00000233146.7::
Pathogenicity Data:
Best Score: 0.372095
REMM: 0.372
Frequency Data:
gnomAD_G_AFR: 0.2775%
gnomAD_G_AMR: 0.4493%
gnomAD_G_NFE: 0.8037%
gnomAD_G_SAS: 0.8913%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 2-47468953-CT-C [0/1] rs71399032
Variant score: 0.231
Transcripts:
MSH2:ENST00000233146.7:c.1662-2011del:p.(=)
Pathogenicity Data:
Best Score: 0.231033
REMM: 0.231
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-47449031-C-A [0/1]
Variant score: 0.132
Transcripts:
MSH2:ENST00000233146.7:c.1386+3374C>A:p.(=)
Pathogenicity Data:
Best Score: 0.132028
REMM: 0.132
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-47449027-C-A [0/1]
Variant score: 0.091
Transcripts:
MSH2:ENST00000233146.7:c.1386+3370C>A:p.(=)
Pathogenicity Data:
Best Score: 0.0908552
REMM: 0.091
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 2-47434523-A-AGGGAGAGGGAGACCGTG [0/1]
Variant score: 0.090
Transcripts:
MSH2:ENST00000233146.7:c.1276+4582_1276+4583insGGGAGAGGGAGACCGTG:p.(=)
Pathogenicity Data:
Best Score: 0.0900742
REMM: 0.090
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 2-47442359-G-GTATATATACACGTATATGTGTATATATATACGTATATATGTGTA [0/1]
ClinVar: BENIGN (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.021
Transcripts:
MSH2:ENST00000233146.7:c.1277-3189_1277-3188insTATATATACACGTATATGTGTATATATATACGTATATATGTGTA:p.(=)
Pathogenicity Data:
Best Score: 0.0208746
REMM: 0.021
Frequency Data:
No frequency data
INTERGENIC_VARIANT INS 2-47502486-T-TATGGATGGATGAATGGATGG [0/1] rs796842506
Variant score: 0.010
Transcripts:
MSH2:ENST00000233146.7::
Pathogenicity Data:
Best Score: 0.0109857
REMM: 0.011
Frequency Data:
gnomAD_G_AFR: 0.3825%
gnomAD_G_AMR: 0.6016%
gnomAD_G_EAS: 0.6238%
gnomAD_G_NFE: 0.1454%
gnomAD_G_SAS: 0.3521%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-47434885-G-A [0/1] rs193082206
Variant score: 0.000
Transcripts:
MSH2:ENST00000233146.7:c.1276+4944G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0024%
gnomAD_G_NFE: 0.0029%
CODING_TRANSCRIPT_INTRON_VARIANT INS 2-47452222-C-CTTTTTTTTTT [0/1] rs572009706
Variant score: 0.000
Transcripts:
MSH2:ENST00000233146.7:c.1386+6565_1386+6566insTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-47482182-C-G [0/1]
Variant score: 0.000
Transcripts:
MSH2:ENST00000233146.7:c.2635-597C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data

CHEK2

Exomiser Score: 0.928 (p=1.8E-3)

Phenotype Score: 0.998

Variant Score: 0.596

Phenotype matches:
Phenotypic similarity 0.998 to Li-Fraumeni syndrome associated with CHEK2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Known diseases:
OMIM:176807 Prostate cancer, somatic - autosomal dominant
OMIM:259500 Osteosarcoma, somatic - somatic
OMIM:609265 Tumor predisposition syndrome 4, breast/prostate/colorectal - autosomal dominant
ORPHA:145 Hereditary breast and/or ovarian cancer syndrome - autosomal dominant
ORPHA:524 Li-Fraumeni syndrome - autosomal dominant
ORPHA:668 Osteosarcoma - somatic
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.928 (p=1.8E-3)

Phenotype Score: 0.998

Variant Score: 0.596

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.998 to ORPHA:524 Li-Fraumeni syndrome
Phenotypic similarity 0.998 to OMIM:609265 Tumor predisposition syndrome 4, breast/prostate/colorectal
Phenotypic similarity 0.998 to ORPHA:145 Hereditary breast and/or ovarian cancer syndrome
Variants contributing to score:
MISSENSE_VARIANT SNV 22-28725277-C-T [0/1] rs368570187
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PP4]
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:1, LB:14, B:1)
Variant score: 0.596 CONTRIBUTING VARIANT
Transcripts:
CHEK2:ENST00000404276.6:c.410G>A:p.(Arg137Gln)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AMR: 0.0425%
gnomAD_E_NFE: 0.0112%
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0197%
gnomAD_G_NFE: 0.0191%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.000 (p=8.7E-1)

Phenotype Score: 0.000

Variant Score: 0.492

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 22-28725277-C-T [0/1] rs368570187
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:1, LB:14, B:1)
Variant score: 0.596 CONTRIBUTING VARIANT
Transcripts:
CHEK2:ENST00000404276.6:c.410G>A:p.(Arg137Gln)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AMR: 0.0425%
gnomAD_E_NFE: 0.0112%
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0197%
gnomAD_G_NFE: 0.0191%
CODING_TRANSCRIPT_INTRON_VARIANT INS 22-28698228-T-TAAAAAAAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.387 CONTRIBUTING VARIANT
Transcripts:
CHEK2:ENST00000404276.6:c.1009-1242_1009-1241insTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.387235
REMM: 0.387
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 22-28729540-CAAAAA-C [0/1]
Variant score: 0.234
Transcripts:
CHEK2:ENST00000404276.6:c.320-4178_320-4174del:p.(=)
Pathogenicity Data:
Best Score: 0.234206
REMM: 0.234
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 22-28721594-T-C [0/1]
Variant score: 0.060
Transcripts:
CHEK2:ENST00000404276.6:c.593-2109A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0602798
REMM: 0.060
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 22-28699362-CT-C [0/1] rs67508991
Variant score: 0.000
Transcripts:
CHEK2:ENST00000404276.6:c.1008+475del:p.(=)
Pathogenicity Data:
Best Score: 2.0E-4
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 22-28693687-C-T [0/1] rs144770665
ClinVar: LIKELY_BENIGN (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.000
Transcripts:
CHEK2:ENST00000404276.6:c.1461+345G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.8992%
gnomAD_G_AFR: 0.1349%
gnomAD_G_AMR: 0.2158%
gnomAD_G_NFE: 0.9383%
gnomAD_G_SAS: 0.0829%

ZBTB20

Exomiser Score: 0.866 (p=2.7E-3)

Phenotype Score: 0.588

Variant Score: 0.984

Phenotype matches:
Phenotypic similarity 0.588 to Primrose syndrome associated with ZBTB20.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Proximity score 0.500 in interactome to PRKN and phenotypic similarity 0.998 to Ovarian cancer, somatic associated with PRKN.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.500 in interactome to PRKN and phenotypic similarity 0.368 to mouse mutant of PRKN.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000160, kyphosis
HP:0006625, Multifocal breast carcinoma - MP:0000160, kyphosis
Known diseases:
OMIM:259050 Primrose syndrome - autosomal dominant
ORPHA:3042 Intellectual disability-cataracts-calcified pinnae-myopathy syndrome - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.866 (p=2.7E-3)

Phenotype Score: 0.588

Variant Score: 0.984

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.588 to OMIM:259050 Primrose syndrome
Phenotypic similarity 0.588 to ORPHA:3042 Intellectual disability-cataracts-calcified pinnae-myopathy syndrome
Variants contributing to score:
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-114624560-C-A [0/1] rs2058542191
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.984 CONTRIBUTING VARIANT
Transcripts:
ZBTB20:ENST00000675478.1:c.-295+68968G>T:p.(=)
Pathogenicity Data:
Best Score: 0.984443
REMM: 0.984
Frequency Data:
gnomAD_G_NFE: 0.0015%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.114 (p=2.5E-1)

Phenotype Score: 0.250

Variant Score: 0.941

No phenotype matches to diseases with this MOI.
Variants contributing to score:
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-114624560-C-A [0/1] rs2058542191
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.984 CONTRIBUTING VARIANT
Transcripts:
ZBTB20:ENST00000675478.1:c.-295+68968G>T:p.(=)
Pathogenicity Data:
Best Score: 0.984443
REMM: 0.984
Frequency Data:
gnomAD_G_NFE: 0.0015%
FIVE_PRIME_UTR_INTRON_VARIANT DEL 3-114453921-TC-T [0/1] rs71616313
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.898 CONTRIBUTING VARIANT
Transcripts:
ZBTB20:ENST00000675478.1:c.-255+46430del:p.(=)
Pathogenicity Data:
Best Score: 0.897839
REMM: 0.898
Frequency Data:
No frequency data
Other passed variants:
FIVE_PRIME_UTR_INTRON_VARIANT INS 3-114880401-G-GAA [0/1] rs540457113
Variant score: 0.864
Transcripts:
ZBTB20:ENST00000675478.1:c.-417+19902_-417+19903insTT:p.(=)
Pathogenicity Data:
Best Score: 0.909251
REMM: 0.909
Frequency Data:
UK10K: 0.0926%
gnomAD_G_AFR: 0.0554%
gnomAD_G_AMR: 0.3141%
gnomAD_G_NFE: 0.1661%
gnomAD_G_SAS: 0.0830%
FIVE_PRIME_UTR_INTRON_VARIANT DEL 3-114904114-AGAGT-A [0/1] rs1179455595
Variant score: 0.742
Transcripts:
ZBTB20:ENST00000675478.1:c.-455-3776_-455-3773del:p.(=)
Pathogenicity Data:
Best Score: 0.742404
REMM: 0.742
Frequency Data:
gnomAD_G_NFE: 0.0015%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-114355677-T-G [0/1] rs115372445
Variant score: 0.702
Transcripts:
ZBTB20:ENST00000675478.1:c.200-3799A>C:p.(=)
Pathogenicity Data:
Best Score: 0.983669
REMM: 0.984
Frequency Data:
UK10K: 1.1373%
gnomAD_G_AFR: 0.2165%
gnomAD_G_AMR: 0.4053%
gnomAD_G_NFE: 1.0408%
gnomAD_G_SAS: 0.4144%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-114954287-G-T [0/1] rs190906183
Variant score: 0.693
Transcripts:
ZBTB20:ENST00000675478.1:c.-456+20079C>A:p.(=)
Pathogenicity Data:
Best Score: 0.705608
REMM: 0.706
Frequency Data:
UK10K: 0.0397%
gnomAD_G_AFR: 0.0120%
gnomAD_G_AMR: 0.0262%
gnomAD_G_NFE: 0.0692%
gnomAD_G_SAS: 0.1245%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-114371855-A-T [0/1] rs1263030520
Variant score: 0.655
Transcripts:
ZBTB20:ENST00000675478.1:c.199+8362T>A:p.(=)
Pathogenicity Data:
Best Score: 0.655573
REMM: 0.656
Frequency Data:
gnomAD_G_NFE: 0.0074%
REGULATORY_REGION_VARIANT SNV 3-115793141-G-A [0/1] rs555727987
Variant score: 0.641
Transcripts:
Pathogenicity Data:
Best Score: 0.651667
REMM: 0.652
Frequency Data:
UK10K: 0.0264%
gnomAD_G_AFR: 0.0144%
gnomAD_G_AMR: 0.1177%
gnomAD_G_NFE: 0.0588%
FIVE_PRIME_UTR_INTRON_VARIANT DEL 3-114805616-ATATAACT-A [0/1] rs1375592587
Variant score: 0.621
Transcripts:
ZBTB20:ENST00000675478.1:c.-416-4449_-416-4443del:p.(=)
Pathogenicity Data:
Best Score: 0.620999
REMM: 0.621
Frequency Data:
gnomAD_G_NFE: 0.0015%
MISSENSE_VARIANT SNV 3-114351462-C-T [0/1] rs779190582
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (LP:1, VUS:1)
Variant score: 0.597
Transcripts:
ZBTB20:ENST00000675478.1:c.616G>A:p.(Asp206Asn)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_SAS: 0.0116%
gnomAD_G_SAS: 0.0415%
FIVE_PRIME_UTR_INTRON_VARIANT DEL 3-114846170-TTG-T [0/1] rs548201976
Variant score: 0.574
Transcripts:
ZBTB20:ENST00000675478.1:c.-416-44998_-416-44997del:p.(=)
Pathogenicity Data:
Best Score: 0.592947
REMM: 0.593
Frequency Data:
UK10K: 0.0397%
gnomAD_G_AFR: 0.0120%
gnomAD_G_AMR: 0.0393%
gnomAD_G_NFE: 0.0706%
gnomAD_G_SAS: 0.2082%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-114879262-C-T [0/1] rs145766015
Variant score: 0.560
Transcripts:
ZBTB20:ENST00000675478.1:c.-417+21042G>A:p.(=)
Pathogenicity Data:
Best Score: 0.575983
REMM: 0.576
Frequency Data:
UK10K: 0.0397%
gnomAD_G_AFR: 0.0120%
gnomAD_G_AMR: 0.0392%
gnomAD_G_NFE: 0.0706%
gnomAD_G_SAS: 0.1866%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-114924245-T-A [0/1] rs867279330
Variant score: 0.547
Transcripts:
ZBTB20:ENST00000675478.1:c.-455-23903A>T:p.(=)
Pathogenicity Data:
Best Score: 0.549076
REMM: 0.549
Frequency Data:
gnomAD_G_AMR: 0.0261%
gnomAD_G_NFE: 0.0103%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-114773511-C-A [0/1] rs866372693
Variant score: 0.506
Transcripts:
ZBTB20:ENST00000675478.1:c.-343+27590G>T:p.(=)
Pathogenicity Data:
Best Score: 0.507803
REMM: 0.508
Frequency Data:
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0262%
gnomAD_G_NFE: 0.0103%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-115096370-C-T [0/1] rs78174224
Variant score: 0.430
Transcripts:
ZBTB20:ENST00000675478.1:c.-702-24956G>A:p.(=)
Pathogenicity Data:
Best Score: 0.633287
REMM: 0.633
Frequency Data:
UK10K: 0.1190%
gnomAD_G_AFR: 1.2164%
gnomAD_G_AMR: 0.5495%
gnomAD_G_NFE: 0.1015%
FIVE_PRIME_UTR_INTRON_VARIANT INS 3-114486137-T-TGTG [1/1]
Variant score: 0.399
Transcripts:
ZBTB20:ENST00000675478.1:c.-255+14214_-255+14215insCAC:p.(=)
Pathogenicity Data:
Best Score: 0.399008
REMM: 0.399
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-114447283-C-A [0/1] rs768867978
Variant score: 0.361
Transcripts:
ZBTB20:ENST00000675478.1:c.-255+53069G>T:p.(=)
Pathogenicity Data:
Best Score: 0.362572
REMM: 0.363
Frequency Data:
UK10K: 0.0264%
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0131%
gnomAD_G_NFE: 0.0088%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-114623589-C-T [0/1] rs149570721
Variant score: 0.346
Transcripts:
ZBTB20:ENST00000675478.1:c.-295+69939G>A:p.(=)
Pathogenicity Data:
Best Score: 0.35481
REMM: 0.355
Frequency Data:
UK10K: 0.0529%
gnomAD_G_AFR: 0.0337%
gnomAD_G_AMR: 0.1700%
gnomAD_G_NFE: 0.1015%
gnomAD_G_SAS: 0.1039%
FIVE_PRIME_UTR_INTRON_VARIANT DEL 3-114959720-TACAC-T [0/1] rs56785871
Variant score: 0.335
Transcripts:
ZBTB20:ENST00000675478.1:c.-456+14642_-456+14645del:p.(=)
Pathogenicity Data:
Best Score: 0.350775
REMM: 0.351
Frequency Data:
gnomAD_G_AFR: 0.2289%
gnomAD_G_AMR: 0.0758%
gnomAD_G_EAS: 0.2064%
gnomAD_G_NFE: 0.0894%
gnomAD_G_SAS: 0.2890%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-115064595-G-T [0/1] rs186934243
Variant score: 0.314
Transcripts:
ZBTB20:ENST00000675478.1:c.-507+6624C>A:p.(=)
Pathogenicity Data:
Best Score: 0.462183
REMM: 0.462
Frequency Data:
UK10K: 0.1058%
gnomAD_G_AFR: 1.2168%
gnomAD_G_AMR: 0.5503%
gnomAD_G_NFE: 0.1016%
FIVE_PRIME_UTR_INTRON_VARIANT DEL 3-114544406-CTTCTTTCTTTCTTTCTTTCTTTCTTTCT-C [0/1]
Variant score: 0.300
Transcripts:
ZBTB20:ENST00000675478.1:c.-294-44043_-294-44016del:p.(=)
Pathogenicity Data:
Best Score: 0.29982
REMM: 0.300
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT DEL 3-115094542-CT-C [0/1] rs1354942721
Variant score: 0.294
Transcripts:
ZBTB20:ENST00000675478.1:c.-702-23129del:p.(=)
Pathogenicity Data:
Best Score: 0.683732
REMM: 0.684
Frequency Data:
gnomAD_G_AFR: 1.6501%
gnomAD_G_AMR: 1.0522%
gnomAD_G_EAS: 0.6927%
gnomAD_G_NFE: 0.6019%
gnomAD_G_SAS: 0.0904%
FIVE_PRIME_UTR_INTRON_VARIANT DEL 3-114831087-CT-C [1/1] rs57265260
Variant score: 0.281
Transcripts:
ZBTB20:ENST00000675478.1:c.-416-29914del:p.(=)
Pathogenicity Data:
Best Score: 0.281025
REMM: 0.281
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT DEL 3-115043629-AATAAT-A [1|0] rs1353932554
Variant score: 0.259
Transcripts:
ZBTB20:ENST00000675478.1:c.-507+27585_-507+27589del:p.(=)
Pathogenicity Data:
Best Score: 0.385819
REMM: 0.386
Frequency Data:
gnomAD_G_AFR: 1.2329%
gnomAD_G_AMR: 0.3933%
gnomAD_G_NFE: 0.0954%
FIVE_PRIME_UTR_INTRON_VARIANT INS 3-114631382-C-CTTTT [0/1] rs66470152
Variant score: 0.257
Transcripts:
ZBTB20:ENST00000675478.1:c.-295+62145_-295+62146insAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.257171
REMM: 0.257
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-114920607-A-G [0/1] rs1283147577
Variant score: 0.227
Transcripts:
ZBTB20:ENST00000675478.1:c.-455-20265T>C:p.(=)
Pathogenicity Data:
Best Score: 0.22724
REMM: 0.227
Frequency Data:
gnomAD_G_NFE: 0.0015%
FIVE_PRIME_UTR_INTRON_VARIANT INS 3-114749568-A-AAAGGAAGGAAGGAAGGAAGGAAGG [0/1] rs71146333
Variant score: 0.209
Transcripts:
ZBTB20:ENST00000675478.1:c.-343+51532_-343+51533insCCTTCCTTCCTTCCTTCCTTCCTT:p.(=)
Pathogenicity Data:
Best Score: 0.217943
REMM: 0.218
Frequency Data:
gnomAD_G_AFR: 0.2590%
gnomAD_G_AMR: 0.0598%
gnomAD_G_NFE: 0.0186%
gnomAD_G_SAS: 0.0497%
FIVE_PRIME_UTR_INTRON_VARIANT INS 3-114748334-C-CTT [0/1] rs762103705
Variant score: 0.180
Transcripts:
ZBTB20:ENST00000675478.1:c.-343+52766_-343+52767insAA:p.(=)
Pathogenicity Data:
Best Score: 0.284688
REMM: 0.285
Frequency Data:
gnomAD_G_AFR: 0.3758%
gnomAD_G_AMR: 1.3139%
gnomAD_G_EAS: 0.9227%
gnomAD_G_NFE: 1.0638%
gnomAD_G_SAS: 0.9339%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-114748352-T-C [0/1]
Variant score: 0.178
Transcripts:
ZBTB20:ENST00000675478.1:c.-343+52749A>G:p.(=)
Pathogenicity Data:
Best Score: 0.177604
REMM: 0.178
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT DEL 3-115036292-AT-A [0/1] rs375496836
Variant score: 0.177
Transcripts:
ZBTB20:ENST00000675478.1:c.-507+34926del:p.(=)
Pathogenicity Data:
Best Score: 0.220237
REMM: 0.220
Frequency Data:
gnomAD_G_AFR: 0.8957%
gnomAD_G_AMR: 0.0396%
gnomAD_G_NFE: 0.0178%
FIVE_PRIME_UTR_INTRON_VARIANT INS 3-114655242-C-CTTTTTT [0/1] rs3085998
Variant score: 0.172
Transcripts:
ZBTB20:ENST00000675478.1:c.-295+38285_-295+38286insAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.172204
REMM: 0.172
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT DEL 3-114948636-CATAG-C [0/1] rs370859544
Variant score: 0.150
Transcripts:
ZBTB20:ENST00000675478.1:c.-456+25726_-456+25729del:p.(=)
Pathogenicity Data:
Best Score: 0.320587
REMM: 0.321
Frequency Data:
UK10K: 0.4232%
gnomAD_G_AFR: 1.5967%
gnomAD_G_AMR: 0.7194%
gnomAD_G_NFE: 0.1064%
gnomAD_G_SAS: 0.0215%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-114817192-T-C [0/1] rs552550692
Variant score: 0.125
Transcripts:
ZBTB20:ENST00000675478.1:c.-416-16018A>G:p.(=)
Pathogenicity Data:
Best Score: 0.357485
REMM: 0.357
Frequency Data:
gnomAD_G_AFR: 0.1626%
gnomAD_G_AMR: 0.3881%
gnomAD_G_NFE: 0.5044%
gnomAD_G_SAS: 1.7587%
FIVE_PRIME_UTR_INTRON_VARIANT DEL 3-114586989-CT-C [0/1] rs1195918426
Variant score: 0.065
Transcripts:
ZBTB20:ENST00000675478.1:c.-294-86599del:p.(=)
Pathogenicity Data:
Best Score: 0.0647365
REMM: 0.065
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 3-114347077-GTT-G [0/1]
Variant score: 0.047
Transcripts:
ZBTB20:ENST00000675478.1:c.1804+3195_1804+3196del:p.(=)
Pathogenicity Data:
Best Score: 0.0466758
REMM: 0.047
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT DEL 3-114409125-CT-C [0/1] rs56339103
Variant score: 0.041
Transcripts:
ZBTB20:ENST00000675478.1:c.-254-20021del:p.(=)
Pathogenicity Data:
Best Score: 0.0405504
REMM: 0.041
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT INS 3-114748380-T-TC [0/1]
Variant score: 0.022
Transcripts:
ZBTB20:ENST00000675478.1:c.-343+52720_-343+52721insG:p.(=)
Pathogenicity Data:
Best Score: 0.0222397
REMM: 0.022
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-114670462-C-T [0/1]
Variant score: 0.011
Transcripts:
ZBTB20:ENST00000675478.1:c.-295+23066G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0114841
REMM: 0.011
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-115090941-T-G [0/1] rs774600715
Variant score: 0.004
Transcripts:
ZBTB20:ENST00000675478.1:c.-702-19527A>C:p.(=)
Pathogenicity Data:
Best Score: 0.00390476
REMM: 0.004
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0131%
gnomAD_G_NFE: 0.0295%
FIVE_PRIME_UTR_INTRON_VARIANT INS 3-114515315-T-TA [0/1] rs566076503
Variant score: 0.003
Transcripts:
ZBTB20:ENST00000675478.1:c.-294-14925_-294-14924insT:p.(=)
Pathogenicity Data:
Best Score: 0.0042
REMM: 0.004
Frequency Data:
UK10K: 0.6083%
gnomAD_G_AFR: 0.1756%
gnomAD_G_AMR: 0.5823%
gnomAD_G_NFE: 0.8438%
gnomAD_G_SAS: 0.5599%
FIVE_PRIME_UTR_INTRON_VARIANT INS 3-114817190-T-TACAC [0/1] rs1491328231
Variant score: 0.000
Transcripts:
ZBTB20:ENST00000675478.1:c.-416-16017_-416-16016insGTGT:p.(=)
Pathogenicity Data:
Best Score: 4.0E-4
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0452%
gnomAD_G_AMR: 0.0792%
gnomAD_G_NFE: 0.1041%
gnomAD_G_SAS: 0.6897%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-114748339-T-C [0|1] rs371610783
Variant score: 0.000
Transcripts:
ZBTB20:ENST00000675478.1:c.-343+52762A>G:p.(=)
Pathogenicity Data:
Best Score: 2.0E-4
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 1.1746%
gnomAD_G_AMR: 1.6462%
gnomAD_G_EAS: 1.2108%
gnomAD_G_NFE: 1.3199%
gnomAD_G_SAS: 1.3523%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-114466693-C-T [0/1] rs144270212
Variant score: 0.000
Transcripts:
ZBTB20:ENST00000675478.1:c.-255+33659G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.9257%
gnomAD_G_AFR: 0.2286%
gnomAD_G_AMR: 0.3007%
gnomAD_G_NFE: 0.6381%
gnomAD_G_SAS: 0.5185%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-114753346-G-A [1|1] rs13078639
Variant score: 0.000
Transcripts:
ZBTB20:ENST00000675478.1:c.-343+47755C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-114778108-A-G [1/1]
Variant score: 0.000
Transcripts:
ZBTB20:ENST00000675478.1:c.-343+22993T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-114859277-T-A [1|1] rs149494005
Variant score: 0.000
Transcripts:
ZBTB20:ENST00000675478.1:c.-417+41027A>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-114859287-T-C [1|1] rs58108681
Variant score: 0.000
Transcripts:
ZBTB20:ENST00000675478.1:c.-417+41017A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-114922803-T-C [0/1] rs529933956
Variant score: 0.000
Transcripts:
ZBTB20:ENST00000675478.1:c.-455-22461A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0421%
gnomAD_G_AMR: 0.0300%
gnomAD_G_NFE: 0.0094%
gnomAD_G_SAS: 0.0555%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-115038769-T-C [0/1] rs142251250
Variant score: 0.000
Transcripts:
ZBTB20:ENST00000675478.1:c.-507+32450A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.1058%
gnomAD_G_AFR: 1.2434%
gnomAD_G_AMR: 0.6926%
gnomAD_G_NFE: 0.1045%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-115073691-T-C [0/1] rs146887177
Variant score: 0.000
Transcripts:
ZBTB20:ENST00000675478.1:c.-702-2277A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.0926%
gnomAD_G_AFR: 1.2220%
gnomAD_G_AMR: 0.5507%
gnomAD_G_NFE: 0.1031%

IGF1R

Exomiser Score: 0.838 (p=3.2E-3)

Phenotype Score: 0.565

Variant Score: 0.987

Phenotype matches:
Phenotypic similarity 0.565 to Growth delay due to insulin-like growth factor I resistance associated with IGF1R.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0006610, Wide intermamillary distance
HP:0006625, Multifocal breast carcinoma - HP:0006610, Wide intermamillary distance
Phenotypic similarity 0.288 to mouse mutant involving IGF1R.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0004289, abnormal bony labyrinth
HP:0006625, Multifocal breast carcinoma - MP:0004289, abnormal bony labyrinth
Proximity score 0.503 in interactome to FGF17 and phenotypic similarity 0.620 to Kallmann syndrome associated with FGF17.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003187, Breast hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0003187, Breast hypoplasia
Known diseases:
OMIM:270450 Insulin-like growth factor I, resistance to - autosomal dominant/recessive
ORPHA:73273 Growth delay due to insulin-like growth factor I resistance - autosomal dominant/recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.838 (p=3.2E-3)

Phenotype Score: 0.565

Variant Score: 0.987

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.565 to ORPHA:73273 Growth delay due to insulin-like growth factor I resistance
Phenotypic similarity 0.559 to OMIM:270450 Insulin-like growth factor I, resistance to
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 15-98650720-G-A [0/1] rs185531477
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.987 CONTRIBUTING VARIANT
Transcripts:
IGF1R:ENST00000650285.1:c.94+1045G>A:p.(=)
Pathogenicity Data:
Best Score: 0.987181
REMM: 0.987
Frequency Data:
gnomAD_G_AFR: 0.0048%
gnomAD_G_NFE: 0.0015%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.778 (p=4.4E-3)

Phenotype Score: 0.565

Variant Score: 0.944

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.565 to ORPHA:73273 Growth delay due to insulin-like growth factor I resistance
Phenotypic similarity 0.559 to OMIM:270450 Insulin-like growth factor I, resistance to
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 15-98650720-G-A [0/1] rs185531477
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.987 CONTRIBUTING VARIANT
Transcripts:
IGF1R:ENST00000650285.1:c.94+1045G>A:p.(=)
Pathogenicity Data:
Best Score: 0.987181
REMM: 0.987
Frequency Data:
gnomAD_G_AFR: 0.0048%
gnomAD_G_NFE: 0.0015%
THREE_PRIME_UTR_EXON_VARIANT DEL 15-98963196-ATGTG-A [0/1] rs774661600
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.901 CONTRIBUTING VARIANT
Transcripts:
IGF1R:ENST00000650285.1:c.*5758_*5761del:p.(=)
Pathogenicity Data:
Best Score: 0.903938
REMM: 0.904
Frequency Data:
gnomAD_E_AFR: 0.0257%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 15-98755718-CAAAAAAA-C [0/1]
Variant score: 0.688
Transcripts:
IGF1R:ENST00000650285.1:c.640+47612_640+47618del:p.(=)
Pathogenicity Data:
Best Score: 0.687501
REMM: 0.688
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 15-98697757-A-AGACAGGTTCTCATTCTGTCACCCAGGCTGGAGTGCAGTGGCGC [0/1] rs372439943
Variant score: 0.674
Transcripts:
IGF1R:ENST00000650285.1:c.95-9805_95-9804insGACAGGTTCTCATTCTGTCACCCAGGCTGGAGTGCAGTGGCGC:p.(=)
Pathogenicity Data:
Best Score: 0.674467
REMM: 0.674
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 15-98755718-C-CAGCAAAAAA [0/1]
Variant score: 0.624
Transcripts:
IGF1R:ENST00000650285.1:c.640+47611_640+47612insAGCAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.62437
REMM: 0.624
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 15-98822492-A-G [0/1] rs149097400
Variant score: 0.584
Transcripts:
IGF1R:ENST00000650285.1:c.641-68833A>G:p.(=)
Pathogenicity Data:
Best Score: 0.755899
REMM: 0.756
Frequency Data:
gnomAD_G_AFR: 0.9847%
gnomAD_G_AMR: 0.0458%
gnomAD_G_NFE: 0.0015%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 15-98673449-GCT-G [0/1] rs148594997
Variant score: 0.512
Transcripts:
IGF1R:ENST00000650285.1:c.94+23775_94+23776del:p.(=)
Pathogenicity Data:
Best Score: 0.804677
REMM: 0.805
Frequency Data:
gnomAD_G_AFR: 1.3043%
gnomAD_G_AMR: 0.1439%
gnomAD_G_NFE: 0.0044%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 15-98693152-C-T [0/1] rs73473457
Variant score: 0.481
Transcripts:
IGF1R:ENST00000650285.1:c.95-14410C>T:p.(=)
Pathogenicity Data:
Best Score: 0.811536
REMM: 0.812
Frequency Data:
gnomAD_G_AFR: 1.3884%
gnomAD_G_AMR: 0.1634%
gnomAD_G_NFE: 0.0029%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 15-98813207-A-C [0/1] rs142665898
Variant score: 0.471
Transcripts:
IGF1R:ENST00000650285.1:c.641-78118A>C:p.(=)
Pathogenicity Data:
Best Score: 0.880718
REMM: 0.881
Frequency Data:
UK10K: 1.4017%
gnomAD_G_AFR: 0.2359%
gnomAD_G_AMR: 1.2289%
gnomAD_G_EAS: 0.0386%
gnomAD_G_NFE: 1.4895%
gnomAD_G_SAS: 0.9516%
CODING_TRANSCRIPT_INTRON_VARIANT INS 15-98768763-C-CAAA [0/1]
Variant score: 0.465
Transcripts:
IGF1R:ENST00000650285.1:c.640+60656_640+60657insAAA:p.(=)
Pathogenicity Data:
Best Score: 0.465132
REMM: 0.465
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 15-98768763-C-CAAAAAA [0/1]
Variant score: 0.465
Transcripts:
IGF1R:ENST00000650285.1:c.640+60656_640+60657insAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.465132
REMM: 0.465
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 15-98845504-T-C [0/1] rs1231911284
Variant score: 0.443
Transcripts:
IGF1R:ENST00000650285.1:c.641-45821T>C:p.(=)
Pathogenicity Data:
Best Score: 0.50931
REMM: 0.509
Frequency Data:
gnomAD_G_AFR: 0.6721%
gnomAD_G_AMR: 0.0256%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 15-98762257-AGATGGAG-A [0|1] rs778759117
Variant score: 0.434
Transcripts:
IGF1R:ENST00000650285.1:c.640+54151_640+54157del:p.(=)
Pathogenicity Data:
Best Score: 0.433519
REMM: 0.434
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 15-98701324-ATTT-A [0/1] rs10581900
Variant score: 0.432
Transcripts:
IGF1R:ENST00000650285.1:c.95-6237_95-6235del:p.(=)
Pathogenicity Data:
Best Score: 0.432056
REMM: 0.432
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 15-98701324-ATTTTT-A [0/1] rs10581900
Variant score: 0.432
Transcripts:
IGF1R:ENST00000650285.1:c.95-6237_95-6233del:p.(=)
Pathogenicity Data:
Best Score: 0.432056
REMM: 0.432
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 15-98733903-A-C [0/1] rs117576967
Variant score: 0.429
Transcripts:
IGF1R:ENST00000650285.1:c.640+25796A>C:p.(=)
Pathogenicity Data:
Best Score: 0.938341
REMM: 0.938
Frequency Data:
UK10K: 1.5340%
gnomAD_G_AFR: 0.2912%
gnomAD_G_AMR: 1.0985%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.6117%
gnomAD_G_SAS: 1.3087%
FIVE_PRIME_UTR_EXON_VARIANT DEL 15-98649520-CTTTTCT-C [0/1] rs1448678288
Variant score: 0.380
Transcripts:
IGF1R:ENST00000650285.1:c.-57_-52del:p.(=)
Pathogenicity Data:
Best Score: 0.386548
REMM: 0.387
Frequency Data:
gnomAD_E_AFR: 0.1182%
gnomAD_E_AMR: 0.0110%
gnomAD_E_EAS: 0.0034%
gnomAD_E_NFE: 0.0004%
UPSTREAM_GENE_VARIANT SNV 15-98643863-G-A [0/1] rs73473410
Variant score: 0.377
Transcripts:
IGF1R:ENST00000650285.1::
Pathogenicity Data:
Best Score: 0.723421
REMM: 0.723
Frequency Data:
gnomAD_G_AFR: 1.5128%
gnomAD_G_AMR: 0.1373%
gnomAD_G_NFE: 0.0029%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 15-98783958-AT-A [0/1]
Variant score: 0.332
Transcripts:
IGF1R:ENST00000650285.1:c.640+75852del:p.(=)
Pathogenicity Data:
Best Score: 0.331813
REMM: 0.332
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT INS 15-98646143-T-TA [0/1] rs151336314
Variant score: 0.325
Transcripts:
IGF1R:ENST00000650285.1::
Pathogenicity Data:
Best Score: 0.569191
REMM: 0.569
Frequency Data:
gnomAD_G_AFR: 1.4293%
gnomAD_G_AMR: 0.1965%
gnomAD_G_EAS: 0.0196%
gnomAD_G_NFE: 0.0406%
gnomAD_G_SAS: 0.0214%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 15-98753098-ATTTG-A [0/1] rs549091684
Variant score: 0.290
Transcripts:
IGF1R:ENST00000650285.1:c.640+44992_640+44995del:p.(=)
Pathogenicity Data:
Best Score: 0.384233
REMM: 0.384
Frequency Data:
gnomAD_G_AFR: 1.0344%
gnomAD_G_AMR: 0.0460%
gnomAD_G_NFE: 0.0015%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 15-98678921-CT-C [0/1] rs60694188
Variant score: 0.288
Transcripts:
IGF1R:ENST00000650285.1:c.95-28640del:p.(=)
Pathogenicity Data:
Best Score: 0.287512
REMM: 0.288
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 15-98845384-C-T [0/1] rs555020819
Variant score: 0.241
Transcripts:
IGF1R:ENST00000650285.1:c.641-45941C>T:p.(=)
Pathogenicity Data:
Best Score: 0.300574
REMM: 0.301
Frequency Data:
gnomAD_G_AFR: 0.9035%
gnomAD_G_AMR: 0.0288%
gnomAD_G_NFE: 0.0016%
CODING_TRANSCRIPT_INTRON_VARIANT INS 15-98878693-A-AAAAAAAACAAC [0/1]
Variant score: 0.151
Transcripts:
IGF1R:ENST00000650285.1:c.641-12632_641-12631insAAAAAAACAAC:p.(=)
Pathogenicity Data:
Best Score: 0.151494
REMM: 0.151
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 15-98675826-C-CTTTCT [0/1] rs1442608280
Variant score: 0.077
Transcripts:
IGF1R:ENST00000650285.1:c.94+26151_94+26152insTTTCT:p.(=)
Pathogenicity Data:
Best Score: 0.102121
REMM: 0.102
Frequency Data:
gnomAD_G_AFR: 1.0406%
gnomAD_G_AMR: 0.2884%
gnomAD_G_NFE: 0.0059%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 15-98689234-CT-C [0/1] rs890361771
Variant score: 0.046
Transcripts:
IGF1R:ENST00000650285.1:c.95-18327del:p.(=)
Pathogenicity Data:
Best Score: 0.0459437
REMM: 0.046
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 15-98628670-C-T [0/1] rs60287478
Variant score: 0.036
Transcripts:
IGF1R:ENST00000650285.1::
Pathogenicity Data:
Best Score: 0.053621
REMM: 0.054
Frequency Data:
gnomAD_G_AFR: 1.2508%
gnomAD_G_AMR: 0.2232%
gnomAD_G_NFE: 0.0177%
gnomAD_G_SAS: 0.0208%
THREE_PRIME_UTR_EXON_VARIANT SNV 15-98958419-C-T [0/1] rs148538142
ClinVar: BENIGN (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.020
Transcripts:
IGF1R:ENST00000650285.1:c.*977C>T:p.(=)
Pathogenicity Data:
Best Score: 0.124942
REMM: 0.125
Frequency Data:
UK10K: 0.0397%
gnomAD_G_AFR: 1.9771%
gnomAD_G_AMR: 0.2027%
gnomAD_G_EAS: 0.0387%
gnomAD_G_NFE: 0.0162%
gnomAD_G_SAS: 0.0207%
THREE_PRIME_UTR_EXON_VARIANT SNV 15-98964227-A-G [0/1] rs184925290
Variant score: 0.016
Transcripts:
IGF1R:ENST00000650285.1:c.*6785A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0161873
REMM: 0.016
Frequency Data:
gnomAD_E_AFR: 0.0540%
gnomAD_E_NFE: 0.0021%
gnomAD_G_AFR: 0.0298%
gnomAD_G_SAS: 0.0209%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 15-98948743-G-A [0/1] rs200279429
Variant score: 0.007
Transcripts:
IGF1R:ENST00000650285.1:c.3722+35G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00666032
REMM: 0.007
Frequency Data:
gnomAD_E_AFR: 0.0209%
gnomAD_E_AMR: 0.0022%
gnomAD_E_NFE: 0.0001%
gnomAD_E_SAS: 0.0012%
gnomAD_G_AFR: 0.0024%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 15-98828547-CAG-C [0/1] rs559684046
Variant score: 0.004
Transcripts:
IGF1R:ENST00000650285.1:c.641-62777_641-62776del:p.(=)
Pathogenicity Data:
Best Score: 0.00547143
REMM: 0.005
Frequency Data:
gnomAD_G_AFR: 0.9701%
gnomAD_G_AMR: 0.0458%
gnomAD_G_NFE: 0.0015%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 15-98798319-C-T [0/1] rs533879900
Variant score: 0.003
Transcripts:
IGF1R:ENST00000650285.1:c.640+90212C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00352857
REMM: 0.004
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0788%
gnomAD_G_NFE: 0.0074%
gnomAD_G_SAS: 0.0423%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 15-98726883-C-A [0/1] rs888413723
Variant score: 0.002
Transcripts:
IGF1R:ENST00000650285.1:c.640+18776C>A:p.(=)
Pathogenicity Data:
Best Score: 0.00253571
REMM: 0.003
Frequency Data:
gnomAD_G_AFR: 0.1277%
gnomAD_G_AMR: 0.0916%
gnomAD_G_SAS: 0.0208%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 15-98747773-C-G [0/1] rs1053086740
Variant score: 0.001
Transcripts:
IGF1R:ENST00000650285.1:c.640+39666C>G:p.(=)
Pathogenicity Data:
Best Score: 0.00114286
REMM: 0.001
Frequency Data:
gnomAD_G_NFE: 0.0044%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 15-98869195-C-T [0/1] rs75113652
Variant score: 0.001
Transcripts:
IGF1R:ENST00000650285.1:c.641-22130C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00142222
REMM: 0.001
Frequency Data:
gnomAD_G_AFR: 1.0430%
gnomAD_G_AMR: 0.0654%
gnomAD_G_NFE: 0.0015%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 15-98693794-T-C [0/1] rs113613768
Variant score: 0.000
Transcripts:
IGF1R:ENST00000650285.1:c.95-13768T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 1.3193%
gnomAD_G_AMR: 0.1439%
gnomAD_G_NFE: 0.0029%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 15-98764665-C-T [0/1] rs148092917
Variant score: 0.000
Transcripts:
IGF1R:ENST00000650285.1:c.640+56558C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.7405%
gnomAD_G_AFR: 0.1323%
gnomAD_G_AMR: 0.4967%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.1291%
gnomAD_G_SAS: 0.8710%
CODING_TRANSCRIPT_INTRON_VARIANT INS 15-98868327-C-CAAAAAAA [0/1]
Variant score: 0.000
Transcripts:
IGF1R:ENST00000650285.1:c.641-22998_641-22997insAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 15-98868327-C-CAAAAAAAA [0/1]
Variant score: 0.000
Transcripts:
IGF1R:ENST00000650285.1:c.641-22998_641-22997insAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 15-98950822-A-G [0/1] rs139050552
Variant score: 0.000
Transcripts:
IGF1R:ENST00000650285.1:c.3722+2114A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 1.1910%
gnomAD_G_AMR: 0.1176%
gnomAD_G_NFE: 0.0029%

CHD7

Exomiser Score: 0.808 (p=3.8E-3)

Phenotype Score: 0.620

Variant Score: 0.902

Phenotype matches:
Phenotypic similarity 0.620 to Kallmann syndrome associated with CHD7.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003187, Breast hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0003187, Breast hypoplasia
Phenotypic similarity 0.330 to mouse mutant involving CHD7.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0011861, increased cranium height
HP:0006625, Multifocal breast carcinoma - MP:0011861, increased cranium height
Phenotypic similarity 0.366 to zebrafish mutant involving CHD7.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0008903, vertebra has fewer parts of type neural spine, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0008903, vertebra has fewer parts of type neural spine, abnormal
Proximity score 0.501 in interactome to FGF8 and phenotypic similarity 0.620 to Kallmann syndrome associated with FGF8.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003187, Breast hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0003187, Breast hypoplasia
Proximity score 0.501 in interactome to FGF8 and phenotypic similarity 0.275 to fish mutant of FGF8.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0010380, chondrocranium bilateral symmetry, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0010380, chondrocranium bilateral symmetry, abnormal
Known diseases:
OMIM:214800 CHARGE syndrome - autosomal dominant
OMIM:612370 Hypogonadotropic hypogonadism 5 with or without anosmia - autosomal dominant
ORPHA:138 CHARGE syndrome - autosomal dominant
ORPHA:39041 Omenn syndrome - autosomal recessive
ORPHA:432 Normosmic congenital hypogonadotropic hypogonadism - autosomal dominant
ORPHA:478 Kallmann syndrome - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.808 (p=3.8E-3)

Phenotype Score: 0.620

Variant Score: 0.902

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.620 to ORPHA:478 Kallmann syndrome
Phenotypic similarity 0.616 to ORPHA:432 Normosmic congenital hypogonadotropic hypogonadism
Phenotypic similarity 0.471 to ORPHA:138 CHARGE syndrome
Phenotypic similarity 0.465 to OMIM:214800 CHARGE syndrome
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-60775366-C-CTACTTTATATGCTTATACTACTTTATATAAGCTTATATGCTTA [0|1] rs71300639
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting, PP4]
Variant score: 0.902 CONTRIBUTING VARIANT
Transcripts:
CHD7:ENST00000423902.7:c.1666-5634_1666-5633insTACTTTATATGCTTATACTACTTTATATAAGCTTATATGCTTA:p.(=)
Pathogenicity Data:
Best Score: 0.901575
REMM: 0.902
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.530 (p=8.1E-2)

Phenotype Score: 0.501

Variant Score: 0.892

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-60775366-C-CTACTTTATATGCTTATACTACTTTATATAAGCTTATATGCTTA [0|1] rs71300639
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.902 CONTRIBUTING VARIANT
Transcripts:
CHD7:ENST00000423902.7:c.1666-5634_1666-5633insTACTTTATATGCTTATACTACTTTATATAAGCTTATATGCTTA:p.(=)
Pathogenicity Data:
Best Score: 0.901575
REMM: 0.902
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT INS 8-60680408-G-GCGGGGGC [0/1] rs1395617336
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.883 CONTRIBUTING VARIANT
Transcripts:
CHD7:ENST00000423902.7:c.-175+1326_-175+1327insCGGGGGC:p.(=)
Pathogenicity Data:
Best Score: 0.883043
REMM: 0.883
Frequency Data:
No frequency data
Other passed variants:
FIVE_PRIME_UTR_INTRON_VARIANT DEL 8-60695004-AG-A [0/1] rs1322187215
Variant score: 0.868
Transcripts:
CHD7:ENST00000423902.7:c.-175+15923del:p.(=)
Pathogenicity Data:
Best Score: 0.870319
REMM: 0.870
Frequency Data:
gnomAD_G_AMR: 0.0066%
gnomAD_G_NFE: 0.0059%
gnomAD_G_SAS: 0.0207%
FIVE_PRIME_UTR_INTRON_VARIANT DEL 8-60680398-CG-C [0/1]
Variant score: 0.845
Transcripts:
CHD7:ENST00000423902.7:c.-175+1317del:p.(=)
Pathogenicity Data:
Best Score: 0.844681
REMM: 0.845
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 8-60703563-G-A [0/1]
Variant score: 0.832
Transcripts:
CHD7:ENST00000423902.7:c.-175+24481G>A:p.(=)
Pathogenicity Data:
Best Score: 0.831813
REMM: 0.832
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-60775363-T-TAAGCTTA [0|1] rs137934348
Variant score: 0.815
Transcripts:
CHD7:ENST00000423902.7:c.1666-5637_1666-5636insAAGCTTA:p.(=)
Pathogenicity Data:
Best Score: 0.815218
REMM: 0.815
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-60771683-CTGGGG-C [1/1] rs879819919
Variant score: 0.787
Transcripts:
CHD7:ENST00000423902.7:c.1666-9316_1666-9312del:p.(=)
Pathogenicity Data:
Best Score: 0.787386
REMM: 0.787
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 8-60680414-G-C [0/1] rs534491218
Variant score: 0.728
Transcripts:
CHD7:ENST00000423902.7:c.-175+1332G>C:p.(=)
Pathogenicity Data:
Best Score: 0.727893
REMM: 0.728
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-60775933-A-ATT [0/1] rs11382482
Variant score: 0.645
Transcripts:
CHD7:ENST00000423902.7:c.1666-5067_1666-5066insTT:p.(=)
Pathogenicity Data:
Best Score: 0.646713
REMM: 0.647
Frequency Data:
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0066%
gnomAD_G_NFE: 0.0059%
gnomAD_G_SAS: 0.0208%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-60744478-ATTT-A [0/1] rs569101482
Variant score: 0.624
Transcripts:
CHD7:ENST00000423902.7:c.1665+1382_1665+1384del:p.(=)
Pathogenicity Data:
Best Score: 0.623988
REMM: 0.624
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT INS 8-60675339-C-CAA [0/1]
Variant score: 0.623
Transcripts:
CHD7:ENST00000423902.7::
Pathogenicity Data:
Best Score: 0.623258
REMM: 0.623
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-60744478-ATT-A [0/1] rs569101482
Variant score: 0.582
Transcripts:
CHD7:ENST00000423902.7:c.1665+1382_1665+1383del:p.(=)
Pathogenicity Data:
Best Score: 0.582245
REMM: 0.582
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 8-60880078-CT-C [0/1] rs71245529
Variant score: 0.326
Transcripts:
CHD7:ENST00000423902.7::
Pathogenicity Data:
Best Score: 0.325885
REMM: 0.326
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 8-60886999-CAA-C [0/1]
Variant score: 0.108
Transcripts:
CHD7:ENST00000423902.7::
Pathogenicity Data:
Best Score: 0.108459
REMM: 0.108
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-60768850-A-G [0/1]
Variant score: 0.020
Transcripts:
CHD7:ENST00000423902.7:c.1666-12150A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0203944
REMM: 0.020
Frequency Data:
No frequency data

ATXN3

Exomiser Score: 0.754 (p=5.4E-3)

Phenotype Score: 0.503

Variant Score: 1.000

Phenotype matches:
Proximity score 0.503 in interactome to PRKN and phenotypic similarity 0.998 to Ovarian cancer, somatic associated with PRKN.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.503 in interactome to PRKN and phenotypic similarity 0.368 to mouse mutant of PRKN.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000160, kyphosis
HP:0006625, Multifocal breast carcinoma - MP:0000160, kyphosis
Known diseases:
OMIM:109150 Machado-Joseph disease - autosomal dominant
OMIM:168600 Parkinson disease, late-onset, susceptibility to (susceptibility)
ORPHA:276238 Machado-Joseph disease type 1 - autosomal dominant
ORPHA:276241 Machado-Joseph disease type 2 - autosomal dominant
ORPHA:276244 Machado-Joseph disease type 3 - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.754 (p=5.4E-3)

Phenotype Score: 0.503

Variant Score: 1.000

No phenotype matches to diseases with this MOI.
Variants contributing to score:
FRAMESHIFT_ELONGATION INS 14-92071010-C-CTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG [0|1] rs1555397062
Exomiser ACMG: LIKELY_PATHOGENIC [PVS1, PM2_Supporting]
Variant score: 1.000 CONTRIBUTING VARIANT
Transcripts:
ATXN3:ENST00000644486.2:c.915_916insCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA:p.(Gly306Glnfs*38)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.002 (p=6.2E-1)

Phenotype Score: 0.251

Variant Score: 0.509

No phenotype matches to diseases with this MOI.
Variants contributing to score:
FRAMESHIFT_ELONGATION INS 14-92071010-C-CTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG [0|1] rs1555397062
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 1.000 CONTRIBUTING VARIANT
Transcripts:
ATXN3:ENST00000644486.2:c.915_916insCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA:p.(Gly306Glnfs*38)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 14-92076939-C-CAAAAAAAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.018 CONTRIBUTING VARIANT
Transcripts:
ATXN3:ENST00000644486.2:c.872+4025_872+4026insTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.0183833
REMM: 0.018
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT INS 14-92074788-C-CAA [0/1] rs1450776578
Variant score: 0.008
Transcripts:
ATXN3:ENST00000644486.2:c.873-3736_873-3735insTT:p.(=)
Pathogenicity Data:
Best Score: 0.00815317
REMM: 0.008
Frequency Data:
gnomAD_G_AFR: 0.0024%
gnomAD_G_NFE: 0.0059%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-92074305-C-T [0/1] rs141580377
Variant score: 0.000
Transcripts:
ATXN3:ENST00000644486.2:c.873-3252G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.0844%
gnomAD_G_AFR: 0.2289%
gnomAD_G_AMR: 0.5440%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 1.4503%
gnomAD_G_SAS: 0.1247%

ARID1B

Exomiser Score: 0.752 (p=5.6E-3)

Phenotype Score: 0.504

Variant Score: 0.998

Phenotype matches:
Phenotypic similarity 0.404 to Coffin-Siris syndrome 1 associated with ARID1B.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000879, Short sternum
HP:0006625, Multifocal breast carcinoma - HP:0000879, Short sternum
Proximity score 0.504 in interactome to TWIST1 and phenotypic similarity 0.998 to Saethre-Chotzen syndrome with or without eyelid anomalies associated with TWIST1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.504 in interactome to TWIST1 and phenotypic similarity 0.356 to mouse mutant of TWIST1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000137, abnormal vertebrae morphology
HP:0006625, Multifocal breast carcinoma - MP:0000137, abnormal vertebrae morphology
Proximity score 0.504 in interactome to TWIST1 and phenotypic similarity 0.257 to fish mutant of TWIST1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0007632, notochord absent, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0007632, notochord absent, abnormal
Known diseases:
OMIM:135900 Coffin-Siris syndrome 1 - autosomal dominant
ORPHA:1465 Coffin-Siris syndrome - autosomal dominant
ORPHA:251056 6q25 microdeletion syndrome (CNV)
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.752 (p=5.6E-3)

Phenotype Score: 0.504

Variant Score: 0.998

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.404 to OMIM:135900 Coffin-Siris syndrome 1
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-157081265-C-T [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.998 CONTRIBUTING VARIANT
Transcripts:
ARID1B:ENST00000636930.2:c.2248-3397C>T:p.(=)
Pathogenicity Data:
Best Score: 0.997667
REMM: 0.998
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.154 (p=2.2E-1)

Phenotype Score: 0.252

Variant Score: 0.976

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-157081265-C-T [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.998 CONTRIBUTING VARIANT
Transcripts:
ARID1B:ENST00000636930.2:c.2248-3397C>T:p.(=)
Pathogenicity Data:
Best Score: 0.997667
REMM: 0.998
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-157097804-C-CT [0/1] rs71558293
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.955 CONTRIBUTING VARIANT
Transcripts:
ARID1B:ENST00000636930.2:c.2492-12668_2492-12667insT:p.(=)
Pathogenicity Data:
Best Score: 0.989565
REMM: 0.990
Frequency Data:
gnomAD_G_AFR: 0.0144%
gnomAD_G_AMR: 0.0261%
gnomAD_G_NFE: 0.0132%
gnomAD_G_SAS: 0.2279%
Other passed variants:
INTERGENIC_VARIANT INS 6-157221309-C-CCCGGTTTCT [0/1] rs587727461
Variant score: 0.927
Transcripts:
ARID1B:ENST00000636930.2::
Pathogenicity Data:
Best Score: 0.945433
REMM: 0.945
Frequency Data:
UK10K: 0.0264%
gnomAD_G_AFR: 0.0337%
gnomAD_G_AMR: 0.0784%
gnomAD_G_EAS: 0.1347%
gnomAD_G_NFE: 0.0838%
gnomAD_G_SAS: 0.1034%
UPSTREAM_GENE_VARIANT SNV 6-156774336-G-A [0|1] rs146032223
Variant score: 0.876
Transcripts:
ARID1B:ENST00000636930.2::
Pathogenicity Data:
Best Score: 0.991357
REMM: 0.991
Frequency Data:
UK10K: 0.4099%
gnomAD_G_AFR: 0.6209%
gnomAD_G_AMR: 0.4250%
gnomAD_G_NFE: 0.6219%
gnomAD_G_SAS: 0.1035%
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-156856802-T-TTGCCTTTGCTTAATGGTAAAATGCA [1|1] rs60089699
Variant score: 0.824
Transcripts:
ARID1B:ENST00000636930.2:c.1986+27381_1986+27382insTGCCTTTGCTTAATGGTAAAATGCA:p.(=)
Pathogenicity Data:
Best Score: 0.824239
REMM: 0.824
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-157108319-T-C [0/1] rs35855139
Variant score: 0.820
Transcripts:
ARID1B:ENST00000636930.2:c.2492-2153T>C:p.(=)
Pathogenicity Data:
Best Score: 0.886736
REMM: 0.887
Frequency Data:
UK10K: 0.4099%
gnomAD_G_AFR: 0.0553%
gnomAD_G_AMR: 0.2876%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.4396%
gnomAD_G_SAS: 0.3314%
INFRAME_INSERTION INS 6-156778982-A-AGGC [0/1] rs797045268
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:1, LB:3, B:2)
Variant score: 0.756
Transcripts:
ARID1B:ENST00000636930.2:c.1318_1320dup:p.(Gly440dup)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 0.4990%
gnomAD_E_AMR: 0.0714%
gnomAD_E_NFE: 0.0712%
gnomAD_E_SAS: 0.0187%
gnomAD_G_AFR: 0.5985%
gnomAD_G_AMR: 0.1684%
gnomAD_G_NFE: 0.0653%
gnomAD_G_SAS: 0.0240%
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-156880775-G-GAAAA [0/1] rs66501584
Variant score: 0.752
Transcripts:
ARID1B:ENST00000636930.2:c.1987-20601_1987-20600insAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.751781
REMM: 0.752
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT DEL 6-156775029-CTTTTA-C [0/1] rs555600358
Variant score: 0.723
Transcripts:
ARID1B:ENST00000636930.2::
Pathogenicity Data:
Best Score: 0.978949
REMM: 0.979
Frequency Data:
UK10K: 0.1058%
gnomAD_G_AFR: 0.0337%
gnomAD_G_AMR: 0.2484%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.2073%
gnomAD_G_SAS: 1.0762%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-157087516-C-A [0/1] rs71578599
Variant score: 0.699
Transcripts:
ARID1B:ENST00000636930.2:c.2491+2611C>A:p.(=)
Pathogenicity Data:
Best Score: 0.700694
REMM: 0.701
Frequency Data:
gnomAD_G_AMR: 0.0131%
gnomAD_G_NFE: 0.0059%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-156845088-A-ATTCG [1/1] rs58136371
Variant score: 0.689
Transcripts:
ARID1B:ENST00000636930.2:c.1986+15667_1986+15668insTTCG:p.(=)
Pathogenicity Data:
Best Score: 0.688755
REMM: 0.689
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-157054223-C-CAAAAAAAAAAAAAA [0/1] rs71645383
Variant score: 0.656
Transcripts:
ARID1B:ENST00000636930.2:c.2248-30439_2248-30438insAAAAAAAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.655776
REMM: 0.656
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-156906546-CAAAAAAAAAAAAAAAAA-C [0/1] rs55660810
Variant score: 0.636
Transcripts:
ARID1B:ENST00000636930.2:c.2136+5022_2136+5038del:p.(=)
Pathogenicity Data:
Best Score: 0.64699
REMM: 0.647
Frequency Data:
gnomAD_G_AFR: 0.1193%
gnomAD_G_AMR: 0.0460%
gnomAD_G_NFE: 0.0153%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-156930919-A-G [0|1] rs1172147797
Variant score: 0.597
Transcripts:
ARID1B:ENST00000636930.2:c.2137-4547A>G:p.(=)
Pathogenicity Data:
Best Score: 0.597467
REMM: 0.597
Frequency Data:
gnomAD_G_NFE: 0.0059%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-156930929-G-A [0|1] rs761284157
Variant score: 0.570
Transcripts:
ARID1B:ENST00000636930.2:c.2137-4537G>A:p.(=)
Pathogenicity Data:
Best Score: 0.571755
REMM: 0.572
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0262%
gnomAD_G_NFE: 0.0059%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-156856700-TCACACACA-T [0/1] rs141705209
Variant score: 0.518
Transcripts:
ARID1B:ENST00000636930.2:c.1986+27280_1986+27287del:p.(=)
Pathogenicity Data:
Best Score: 0.517572
REMM: 0.518
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-157010175-T-C [0/1] rs35704002
Variant score: 0.494
Transcripts:
ARID1B:ENST00000636930.2:c.2248-74487T>C:p.(=)
Pathogenicity Data:
Best Score: 0.642367
REMM: 0.642
Frequency Data:
UK10K: 0.1322%
gnomAD_G_AFR: 0.0529%
gnomAD_G_AMR: 0.4507%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.2794%
gnomAD_G_SAS: 0.9975%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-156976999-C-T [0/1] rs35063756
Variant score: 0.479
Transcripts:
ARID1B:ENST00000636930.2:c.2247+41423C>T:p.(=)
Pathogenicity Data:
Best Score: 0.650971
REMM: 0.651
Frequency Data:
UK10K: 0.1322%
gnomAD_E_AFR: 0.0695%
gnomAD_E_AMR: 0.2428%
gnomAD_E_EAS: 0.0141%
gnomAD_E_NFE: 0.2409%
gnomAD_E_SAS: 0.7838%
gnomAD_G_AFR: 0.0534%
gnomAD_G_AMR: 0.4304%
gnomAD_G_EAS: 0.0388%
gnomAD_G_NFE: 0.2693%
gnomAD_G_SAS: 1.0820%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-157102604-CTT-C [0/1] rs35977420
Variant score: 0.442
Transcripts:
ARID1B:ENST00000636930.2:c.2492-7867_2492-7866del:p.(=)
Pathogenicity Data:
Best Score: 0.441992
REMM: 0.442
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-157147253-A-AC [0/1]
Variant score: 0.405
Transcripts:
ARID1B:ENST00000636930.2:c.2762-1371_2762-1370insC:p.(=)
Pathogenicity Data:
Best Score: 0.40499
REMM: 0.405
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-157114523-CA-C [0/1]
Variant score: 0.380
Transcripts:
ARID1B:ENST00000636930.2:c.2581+3963del:p.(=)
Pathogenicity Data:
Best Score: 0.379681
REMM: 0.380
Frequency Data:
No frequency data
INTERGENIC_VARIANT INS 6-156761713-A-AAC [0/1]
Variant score: 0.380
Transcripts:
ARID1B:ENST00000636930.2::
Pathogenicity Data:
Best Score: 0.379504
REMM: 0.380
Frequency Data:
No frequency data
DOWNSTREAM_GENE_VARIANT INS 6-157213166-A-AGTAAAACGTCTTAGTCCATTGAAGGCCTGTATTTGGCACTAAATACTAAATACTAAATTTAGTGCCAATACAGGCCTTCAATGGACTAAGCCGTTGTACT [1/1]
Variant score: 0.344
Transcripts:
ARID1B:ENST00000636930.2::
Pathogenicity Data:
Best Score: 0.344243
REMM: 0.344
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-157004897-C-CTTTTTTT [0/1] rs1177807875
Variant score: 0.260
Transcripts:
ARID1B:ENST00000636930.2:c.2247+69321_2247+69322insTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.266487
REMM: 0.266
Frequency Data:
gnomAD_G_AFR: 0.0506%
gnomAD_G_AMR: 0.1147%
gnomAD_G_EAS: 0.1118%
gnomAD_G_NFE: 0.1615%
gnomAD_G_SAS: 0.0448%
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-157018212-C-CTTTT [0/1] rs1208883079
Variant score: 0.191
Transcripts:
ARID1B:ENST00000636930.2:c.2248-66450_2248-66449insTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.191457
REMM: 0.191
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-157039322-C-CTTTTTTTTTTTTTTTTTTTT [0/1]
Variant score: 0.188
Transcripts:
ARID1B:ENST00000636930.2:c.2248-45340_2248-45339insTTTTTTTTTTTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.195246
REMM: 0.195
Frequency Data:
gnomAD_G_AFR: 0.0850%
gnomAD_G_AMR: 0.1845%
gnomAD_G_EAS: 0.1024%
gnomAD_G_NFE: 0.2395%
gnomAD_G_SAS: 0.0273%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-157147402-A-C [0/1]
Variant score: 0.186
Transcripts:
ARID1B:ENST00000636930.2:c.2762-1222A>C:p.(=)
Pathogenicity Data:
Best Score: 0.186025
REMM: 0.186
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-157147595-G-T [1/1]
Variant score: 0.179
Transcripts:
ARID1B:ENST00000636930.2:c.2762-1029G>T:p.(=)
Pathogenicity Data:
Best Score: 0.178817
REMM: 0.179
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-157147217-T-G [1/1]
Variant score: 0.171
Transcripts:
ARID1B:ENST00000636930.2:c.2762-1407T>G:p.(=)
Pathogenicity Data:
Best Score: 0.171476
REMM: 0.171
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-157164699-C-T [0/1] rs533869385
Variant score: 0.156
Transcripts:
ARID1B:ENST00000636930.2:c.3090-2341C>T:p.(=)
Pathogenicity Data:
Best Score: 0.653213
REMM: 0.653
Frequency Data:
UK10K: 0.0529%
gnomAD_G_AFR: 0.0241%
gnomAD_G_AMR: 0.2094%
gnomAD_G_NFE: 0.1088%
gnomAD_G_SAS: 1.8911%
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-157060630-C-CT [0/1] rs56870548
Variant score: 0.149
Transcripts:
ARID1B:ENST00000636930.2:c.2248-24032_2248-24031insT:p.(=)
Pathogenicity Data:
Best Score: 0.148588
REMM: 0.149
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-157060630-CTTT-C [0/1] rs56870548
Variant score: 0.149
Transcripts:
ARID1B:ENST00000636930.2:c.2248-24031_2248-24029del:p.(=)
Pathogenicity Data:
Best Score: 0.148588
REMM: 0.149
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-157147246-G-A [0/1]
Variant score: 0.147
Transcripts:
ARID1B:ENST00000636930.2:c.2762-1378G>A:p.(=)
Pathogenicity Data:
Best Score: 0.14728
REMM: 0.147
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-157147251-C-T [0/1]
Variant score: 0.140
Transcripts:
ARID1B:ENST00000636930.2:c.2762-1373C>T:p.(=)
Pathogenicity Data:
Best Score: 0.140177
REMM: 0.140
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-156945233-C-CTTTT [1/1] rs1164805779
Variant score: 0.131
Transcripts:
ARID1B:ENST00000636930.2:c.2247+9657_2247+9658insTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.175966
REMM: 0.176
Frequency Data:
gnomAD_G_AFR: 0.4161%
gnomAD_G_AMR: 0.5802%
gnomAD_G_EAS: 0.8152%
gnomAD_G_NFE: 1.0619%
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-156838709-T-TATAATAATAATAATA [0/1] rs35310749
Variant score: 0.113
Transcripts:
ARID1B:ENST00000636930.2:c.1986+9288_1986+9289insATAATAATAATAATA:p.(=)
Pathogenicity Data:
Best Score: 0.154232
REMM: 0.154
Frequency Data:
gnomAD_G_AFR: 0.8980%
gnomAD_G_AMR: 0.7605%
gnomAD_G_EAS: 0.3745%
gnomAD_G_NFE: 0.5283%
gnomAD_G_SAS: 1.0903%
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-156897264-C-CTTCTTCTTCTTCTTCTTCTTA [0/1] rs71027320
Variant score: 0.098
Transcripts:
ARID1B:ENST00000636930.2:c.1987-4112_1987-4111insTTCTTCTTCTTCTTCTTCTTA:p.(=)
Pathogenicity Data:
Best Score: 0.103083
REMM: 0.103
Frequency Data:
gnomAD_G_AFR: 0.0686%
gnomAD_G_AMR: 0.1668%
gnomAD_G_EAS: 0.0591%
gnomAD_G_NFE: 0.2859%
gnomAD_G_SAS: 0.1855%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-156865192-G-A [0/1] rs559497857
Variant score: 0.087
Transcripts:
ARID1B:ENST00000636930.2:c.1986+35771G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0882837
REMM: 0.088
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AFR: 0.0096%
gnomAD_G_AMR: 0.0196%
gnomAD_G_NFE: 0.0191%
gnomAD_G_SAS: 0.0831%
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-156897264-C-CTTCTTCTTCTTA [0/1] rs71027320
Variant score: 0.083
Transcripts:
ARID1B:ENST00000636930.2:c.1987-4112_1987-4111insTTCTTCTTCTTA:p.(=)
Pathogenicity Data:
Best Score: 0.103083
REMM: 0.103
Frequency Data:
gnomAD_G_AFR: 0.5769%
gnomAD_G_AMR: 0.8618%
gnomAD_G_EAS: 0.8865%
gnomAD_G_NFE: 0.7641%
gnomAD_G_SAS: 0.7428%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-157039676-TCCTTCCTTCCTTCCTTCC-T [0|1] rs777533253
Variant score: 0.027
Transcripts:
ARID1B:ENST00000636930.2:c.2248-44985_2248-44968del:p.(=)
Pathogenicity Data:
Best Score: 0.0469798
REMM: 0.047
Frequency Data:
gnomAD_G_AFR: 0.5888%
gnomAD_G_AMR: 0.9143%
gnomAD_G_NFE: 1.4280%
gnomAD_G_SAS: 0.2609%
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-157004631-T-TA [0/1] rs148943158
Variant score: 0.007
Transcripts:
ARID1B:ENST00000636930.2:c.2247+69055_2247+69056insA:p.(=)
Pathogenicity Data:
Best Score: 0.00950397
REMM: 0.010
Frequency Data:
UK10K: 0.1455%
gnomAD_G_AFR: 0.0505%
gnomAD_G_AMR: 0.4448%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.2822%
gnomAD_G_SAS: 1.0145%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-156827754-CT-C [0/1] rs532857305
Variant score: 0.007
Transcripts:
ARID1B:ENST00000636930.2:c.1792-1472del:p.(=)
Pathogenicity Data:
Best Score: 0.00704325
REMM: 0.007
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-156794570-CT-C [0/1] rs34848808
Variant score: 0.005
Transcripts:
ARID1B:ENST00000636930.2:c.1791+15100del:p.(=)
Pathogenicity Data:
Best Score: 0.005
REMM: 0.005
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-156961140-C-A [0/1] rs34543459
Variant score: 0.005
Transcripts:
ARID1B:ENST00000636930.2:c.2247+25564C>A:p.(=)
Pathogenicity Data:
Best Score: 0.00489365
REMM: 0.005
Frequency Data:
gnomAD_G_NFE: 0.0073%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-156950607-G-A [0/1] rs71578592
Variant score: 0.003
Transcripts:
ARID1B:ENST00000636930.2:c.2247+15031G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00529325
REMM: 0.005
Frequency Data:
gnomAD_G_AFR: 0.7640%
gnomAD_G_AMR: 1.0837%
gnomAD_G_EAS: 0.0348%
gnomAD_G_NFE: 0.5527%
gnomAD_G_SAS: 1.5389%
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-157000696-C-CTTTTTTTT [0/1] rs10536002
Variant score: 0.002
Transcripts:
ARID1B:ENST00000636930.2:c.2247+65120_2247+65121insTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.0017
REMM: 0.002
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-157200065-C-T [0/1] rs147981994
Variant score: 0.001
Transcripts:
ARID1B:ENST00000636930.2:c.4480-640C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00117302
REMM: 0.001
Frequency Data:
UK10K: 1.5340%
gnomAD_G_AFR: 0.2695%
gnomAD_G_AMR: 0.7777%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.4143%
gnomAD_G_SAS: 0.5182%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-156981986-C-T [0/1] rs71578593
Variant score: 0.000
Transcripts:
ARID1B:ENST00000636930.2:c.2247+46410C>T:p.(=)
Pathogenicity Data:
Best Score: 1.42857E-4
REMM: 0.000
Frequency Data:
UK10K: 0.1322%
gnomAD_G_AFR: 0.0628%
gnomAD_G_AMR: 0.4391%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.2752%
gnomAD_G_SAS: 1.1051%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-157052789-G-A [0/1] rs35901367
Variant score: 0.000
Transcripts:
ARID1B:ENST00000636930.2:c.2248-31873G>A:p.(=)
Pathogenicity Data:
Best Score: 1.11111E-4
REMM: 0.000
Frequency Data:
UK10K: 0.1455%
gnomAD_G_AFR: 0.0554%
gnomAD_G_AMR: 0.4446%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.2705%
gnomAD_G_SAS: 1.0382%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-156843364-A-G [0/1] rs13205041
Variant score: 0.000
Transcripts:
ARID1B:ENST00000636930.2:c.1986+13943A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.0793%
gnomAD_G_AFR: 0.0481%
gnomAD_G_AMR: 0.2352%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.1881%
gnomAD_G_SAS: 1.2220%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-156930917-A-G [0|1] rs1461298761
Variant score: 0.000
Transcripts:
ARID1B:ENST00000636930.2:c.2137-4549A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_NFE: 0.0044%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-156930918-G-C [0|1] rs1032691362
Variant score: 0.000
Transcripts:
ARID1B:ENST00000636930.2:c.2137-4548G>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0024%
gnomAD_G_NFE: 0.0074%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-156930928-T-C [0|1] rs533430429
Variant score: 0.000
Transcripts:
ARID1B:ENST00000636930.2:c.2137-4538T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AFR: 0.0168%
gnomAD_G_AMR: 0.0654%
gnomAD_G_EAS: 0.1736%
gnomAD_G_NFE: 0.0162%

CFTR

Exomiser Score: 0.752 (p=5.7E-3)

Phenotype Score: 0.501

Variant Score: 1.000

Phenotype matches:
Phenotypic similarity 0.274 to mouse mutant involving CFTR.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002240, abnormal paranasal sinus morphology
HP:0006625, Multifocal breast carcinoma - MP:0002240, abnormal paranasal sinus morphology
Proximity score 0.501 in interactome to FOXA2 and phenotypic similarity 0.676 to Combined pituitary hormone deficiencies, genetic forms associated with FOXA2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
HP:0006625, Multifocal breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
Proximity score 0.501 in interactome to FOXA2 and phenotypic similarity 0.293 to mouse mutant of FOXA2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000932, absent notochord
HP:0006625, Multifocal breast carcinoma - MP:0000932, absent notochord
Known diseases:
OMIM:167800 Pancreatitis, hereditary (susceptibility)
OMIM:211400 Bronchiectasis with or without elevated sweat chloride 1, modifier of (susceptibility)
OMIM:219700 Cystic fibrosis - autosomal recessive
OMIM:277180 Congenital bilateral absence of vas deferens - autosomal recessive
ORPHA:399805 Male infertility with azoospermia or oligozoospermia due to single gene mutation (susceptibility)
ORPHA:48 Congenital bilateral absence of vas deferens - autosomal recessive
ORPHA:586 Cystic fibrosis - autosomal recessive
ORPHA:60033 Idiopathic bronchiectasis - autosomal dominant
ORPHA:676 Hereditary chronic pancreatitis - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.752 (p=5.7E-3)

Phenotype Score: 0.501

Variant Score: 1.000

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 7-117540270-G-C [0/1] rs77932196
Exomiser ACMG: PATHOGENIC [PM1_Supporting, PM5, PP5_VeryStrong]
ClinVar: PATHOGENIC (PRACTICE_GUIDELINE)
Variant score: 1.000 CONTRIBUTING VARIANT WHITELIST VARIANT
Transcripts:
CFTR:ENST00000003084.11:c.1040G>C:p.(Arg347Pro)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_NFE: 0.0054%
gnomAD_G_AFR: 0.0024%
gnomAD_G_NFE: 0.0029%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.298 (p=1.6E-1)

Phenotype Score: 0.501

Variant Score: 0.786

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 7-117540270-G-C [0/1] rs77932196
Exomiser ACMG: PATHOGENIC [PM1_Supporting, PM2_Supporting, PM5, PP5_VeryStrong]
ClinVar: PATHOGENIC (PRACTICE_GUIDELINE)
Variant score: 1.000 CONTRIBUTING VARIANT WHITELIST VARIANT
Transcripts:
CFTR:ENST00000003084.11:c.1040G>C:p.(Arg347Pro)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_NFE: 0.0054%
gnomAD_G_AFR: 0.0024%
gnomAD_G_NFE: 0.0029%
INTERGENIC_VARIANT SNV 7-117687973-G-T [0/1] rs558515966
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.572 CONTRIBUTING VARIANT
Transcripts:
CFTR:ENST00000003084.11::
Pathogenicity Data:
Best Score: 0.593394
REMM: 0.593
Frequency Data:
UK10K: 0.0529%
gnomAD_G_AMR: 0.2332%
gnomAD_G_NFE: 0.0729%
gnomAD_G_SAS: 0.1979%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-117512633-CA-C [0/1] rs5886861
Variant score: 0.444
Transcripts:
CFTR:ENST00000003084.11:c.273+3492del:p.(=)
Pathogenicity Data:
Best Score: 0.443935
REMM: 0.444
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-117556512-CT-C [1/1] rs55700428
Variant score: 0.259
Transcripts:
CFTR:ENST00000003084.11:c.1393-2951del:p.(=)
Pathogenicity Data:
Best Score: 0.258695
REMM: 0.259
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-117526735-C-T [0/1] rs213940
Variant score: 0.024
Transcripts:
CFTR:ENST00000003084.11:c.274-4164C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0238909
REMM: 0.024
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-117621341-A-G [0/1]
Variant score: 0.019
Transcripts:
CFTR:ENST00000003084.11:c.3469-6181A>G:p.(=)
Pathogenicity Data:
Best Score: 0.018856
REMM: 0.019
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-117525304-A-G [0/1]
Variant score: 0.016
Transcripts:
CFTR:ENST00000003084.11:c.274-5595A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0160337
REMM: 0.016
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-117564870-T-G [0/1] rs1378206026
Variant score: 0.009
Transcripts:
CFTR:ENST00000003084.11:c.1584+5215T>G:p.(=)
Pathogenicity Data:
Best Score: 0.0085881
REMM: 0.009
Frequency Data:
gnomAD_G_NFE: 0.0059%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-117529217-A-G [0/1] rs213941
Variant score: 0.007
Transcripts:
CFTR:ENST00000003084.11:c.274-1682A>G:p.(=)
Pathogenicity Data:
Best Score: 0.00721984
REMM: 0.007
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-117646246-T-G [0/1] rs900539321
Variant score: 0.002
Transcripts:
CFTR:ENST00000003084.11:c.3873+3653T>G:p.(=)
Pathogenicity Data:
Best Score: 0.00214286
REMM: 0.002
Frequency Data:
gnomAD_G_NFE: 0.0044%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-117612702-A-G [0/1] rs117004361
Variant score: 0.001
Transcripts:
CFTR:ENST00000003084.11:c.3367+894A>G:p.(=)
Pathogenicity Data:
Best Score: 0.00110278
REMM: 0.001
Frequency Data:
UK10K: 0.8199%
gnomAD_G_AFR: 0.1203%
gnomAD_G_AMR: 0.0589%
gnomAD_G_NFE: 0.6470%
gnomAD_G_SAS: 0.0414%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-117583323-C-G [0/1] rs113183139
Variant score: 0.000
Transcripts:
CFTR:ENST00000003084.11:c.1585-4416C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.9389%
gnomAD_G_AFR: 0.1667%
gnomAD_G_AMR: 0.1510%
gnomAD_G_NFE: 0.8710%
gnomAD_G_SAS: 0.3744%

MUC4

Exomiser Score: 0.751 (p=5.7E-3)

Phenotype Score: 0.501

Variant Score: 1.000

Phenotype matches:
Proximity score 0.501 in interactome to ERBB2 and phenotypic similarity 0.998 to Ovarian cancer, somatic associated with ERBB2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.751 (p=5.7E-3)

Phenotype Score: 0.501

Variant Score: 1.000

No phenotype matches to diseases with this MOI.
Variants contributing to score:
FRAMESHIFT_TRUNCATION DEL 3-195780022-TCACC-T [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 1.000 CONTRIBUTING VARIANT
Transcripts:
MUC4:ENST00000463781.8:c.11554_11557del:p.(Gly3852Thrfs*406)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.603 (p=5.8E-2)

Phenotype Score: 0.501

Variant Score: 0.925

No phenotype matches to diseases with this MOI.
Variants contributing to score:
FRAMESHIFT_TRUNCATION DEL 3-195780022-TCACC-T [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 1.000 CONTRIBUTING VARIANT
Transcripts:
MUC4:ENST00000463781.8:c.11554_11557del:p.(Gly3852Thrfs*406)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
INFRAME_INSERTION INS 3-195780371-C-CTGAGGAAGGGCTGGTGACATGAAGAGGGGTGACGTGACCTGTAGATACTGAGGAAGTGCTGGTGACAGGAAGAGGGGTGGCCTGACCTGTGGATGA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting, PM4]
Variant score: 0.850 CONTRIBUTING VARIANT
Transcripts:
MUC4:ENST00000463781.8:c.11208_11209insTCATCCACAGGTCAGGCCACCCCTCTTCCTGTCACCAGCACTTCCTCAGTATCTACAGGTCACGTCACCCCTCTTCATGTCACCAGCCCTTCCTCA:p.(Ser3736_Ala3737insSerSerThrGlyGlnAlaThrProLeuProValThrSerThrSerSerValSerThrGlyHisValThrProLeuHisValThrSerProSerSer)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
Other passed variants:
INFRAME_INSERTION INS 3-195788543-T-TGGTGACAGGAAGAGGGGTGGCGTGACCTGTGGATTCTGAGGAAGTGTC [0/1]
Variant score: 0.850
Transcripts:
MUC4:ENST00000463781.8:c.3036_3037insGACACTTCCTCAGAATCCACAGGTCACGCCACCCCTCTTCCTGTCACC:p.(Thr1012_Ser1013insAspThrSerSerGluSerThrGlyHisAlaThrProLeuProValThr)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 3-195749306-TTTCCTAGGGAAAAAGG-T [0/1] rs58402120
Variant score: 0.746
Transcripts:
MUC4:ENST00000463781.8:c.15872-258_15872-243del:p.(=)
Pathogenicity Data:
Best Score: 0.745508
REMM: 0.746
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 3-195750137-CCTGTTCT-C [0|1]
Variant score: 0.735
Transcripts:
MUC4:ENST00000463781.8:c.15871+745_15871+751del:p.(=)
Pathogenicity Data:
Best Score: 0.734844
REMM: 0.735
Frequency Data:
No frequency data
FRAMESHIFT_VARIANT INS 3-195783379-G-GCC [0|1] rs778652492
Variant score: 0.680
Transcripts:
MUC4:ENST00000463781.8:c.8200_8201insGG:p.(Thr2734Argfs*271)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_G_AFR: 0.4508%
gnomAD_G_AMR: 0.6747%
gnomAD_G_EAS: 1.2132%
gnomAD_G_NFE: 1.0101%
CODING_TRANSCRIPT_INTRON_VARIANT INS 3-195799260-T-TGTGTGAGAGA [0|1] rs1553889795
Variant score: 0.631
Transcripts:
MUC4:ENST00000463781.8:c.83-7764_83-7763insTCTCTCACAC:p.(=)
Pathogenicity Data:
Best Score: 0.645984
REMM: 0.646
Frequency Data:
gnomAD_G_AFR: 0.0224%
gnomAD_G_AMR: 0.0398%
gnomAD_G_EAS: 0.1579%
gnomAD_G_NFE: 0.0564%
gnomAD_G_SAS: 0.0631%
MISSENSE_VARIANT SNV 3-195778964-C-T [0/1] rs58500707
Variant score: 0.600
Transcripts:
MUC4:ENST00000463781.8:c.12616G>A:p.(Ala4206Thr)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 3-195778967-G-C [0/1] rs59101491
Variant score: 0.600
Transcripts:
MUC4:ENST00000463781.8:c.12613C>G:p.(His4205Asp)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 3-195779012-T-C [0/1] rs200813870
Variant score: 0.600
Transcripts:
MUC4:ENST00000463781.8:c.12568A>G:p.(Thr4190Ala)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 3-195779084-C-T [0/1] rs55789594
Variant score: 0.600
Transcripts:
MUC4:ENST00000463781.8:c.12496G>A:p.(Ala4166Thr)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 3-195779089-G-C [0/1] rs112020305
Variant score: 0.600
Transcripts:
MUC4:ENST00000463781.8:c.12491C>G:p.(Thr4164Ser)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 3-195779423-T-C [0/1] rs202208985
Variant score: 0.600
Transcripts:
MUC4:ENST00000463781.8:c.12157A>G:p.(Asn4053Asp)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 3-195779589-G-C [0/1] rs113130007
Variant score: 0.600
Transcripts:
MUC4:ENST00000463781.8:c.11991C>G:p.(His3997Gln)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 3-195779821-C-A [0/1]
Variant score: 0.600
Transcripts:
MUC4:ENST00000463781.8:c.11759G>T:p.(Arg3920Leu)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 3-195780322-G-A [0/1] rs201474621
Variant score: 0.600
Transcripts:
MUC4:ENST00000463781.8:c.11258C>T:p.(Ala3753Val)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 3-195780334-C-T [0/1] rs745444698
Variant score: 0.600
Transcripts:
MUC4:ENST00000463781.8:c.11246G>A:p.(Ser3749Asn)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 3-195780335-T-C [0/1] rs757870055
Variant score: 0.600
Transcripts:
MUC4:ENST00000463781.8:c.11245A>G:p.(Ser3749Gly)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 3-195783908-C-T [0/1] rs767867174
Variant score: 0.600
Transcripts:
MUC4:ENST00000463781.8:c.7672G>A:p.(Ala2558Thr)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 3-195785696-G-A [0/1] rs150659095
Variant score: 0.600
Transcripts:
MUC4:ENST00000463781.8:c.5884C>T:p.(Pro1962Ser)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 3-195787862-C-A [0|1] rs201433788
ClinVar: BENIGN (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.600
Transcripts:
MUC4:ENST00000463781.8:c.3718G>T:p.(Ala1240Ser)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 3-195787897-T-C [0|1] rs199530228
Variant score: 0.600
Transcripts:
MUC4:ENST00000463781.8:c.3683A>G:p.(Asp1228Gly)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 3-195788482-T-G [0/1] rs13065435
Variant score: 0.600
Transcripts:
MUC4:ENST00000463781.8:c.3098A>C:p.(Glu1033Ala)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 3-195783355-G-C [0/1] rs1560342971
Variant score: 0.600
Transcripts:
MUC4:ENST00000463781.8:c.8225C>G:p.(Thr2742Ser)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_NFE: 0.0001%
MISSENSE_VARIANT SNV 3-195779026-G-A [0/1] rs149026852
Variant score: 0.597
Transcripts:
MUC4:ENST00000463781.8:c.12554C>T:p.(Ala4185Val)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_G_AFR: 0.0127%
gnomAD_G_AMR: 0.0092%
gnomAD_G_EAS: 0.0392%
gnomAD_G_NFE: 0.0063%
gnomAD_G_SAS: 0.0327%
MISSENSE_VARIANT SNV 3-195784685-T-A [0/1] rs79961534
Variant score: 0.596
Transcripts:
MUC4:ENST00000463781.8:c.6895A>T:p.(Thr2299Ser)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_G_NFE: 0.0459%
MISSENSE_VARIANT SNV 3-195783029-C-T [0|1] rs557314271
Variant score: 0.596
Transcripts:
MUC4:ENST00000463781.8:c.8551G>A:p.(Val2851Ile)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_EAS: 0.0474%
gnomAD_E_NFE: 0.0132%
gnomAD_G_NFE: 0.0104%
MISSENSE_VARIANT SNV 3-195790543-G-A [0/1] rs201530979
Variant score: 0.592
Transcripts:
MUC4:ENST00000463781.8:c.1037C>T:p.(Pro346Leu)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.0132%
gnomAD_E_AFR: 0.0090%
gnomAD_E_AMR: 0.0604%
gnomAD_E_EAS: 0.0050%
gnomAD_E_NFE: 0.0667%
gnomAD_E_SAS: 0.0185%
gnomAD_G_AFR: 0.0072%
gnomAD_G_AMR: 0.0915%
gnomAD_G_NFE: 0.0706%
gnomAD_G_SAS: 0.0207%
MISSENSE_VARIANT SNV 3-195783839-T-C [0/1] rs75657645
Variant score: 0.591
Transcripts:
MUC4:ENST00000463781.8:c.7741A>G:p.(Ser2581Gly)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_G_AFR: 0.1098%
gnomAD_G_AMR: 0.0310%
gnomAD_G_EAS: 0.0407%
gnomAD_G_NFE: 0.0394%
gnomAD_G_SAS: 0.0547%
MISSENSE_VARIANT SNV 3-195779036-T-C [0/1] rs138720131
Variant score: 0.589
Transcripts:
MUC4:ENST00000463781.8:c.12544A>G:p.(Thr4182Ala)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 0.0135%
gnomAD_E_AMR: 0.0499%
gnomAD_E_EAS: 0.0321%
gnomAD_E_NFE: 0.0254%
gnomAD_E_SAS: 0.0116%
gnomAD_G_AFR: 0.0310%
gnomAD_G_AMR: 0.0323%
gnomAD_G_NFE: 0.0763%
gnomAD_G_SAS: 0.1272%
MISSENSE_VARIANT SNV 3-195780908-C-T [0/1] rs202084932
Variant score: 0.581
Transcripts:
MUC4:ENST00000463781.8:c.10672G>A:p.(Ala3558Thr)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_G_AFR: 0.2067%
gnomAD_G_AMR: 0.0538%
gnomAD_G_EAS: 0.0633%
gnomAD_G_NFE: 0.0434%
MISSENSE_VARIANT SNV 3-195784676-C-T [0/1] rs74542179
Variant score: 0.570
Transcripts:
MUC4:ENST00000463781.8:c.6904G>A:p.(Ala2302Thr)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_G_AFR: 0.1926%
gnomAD_G_AMR: 0.1251%
gnomAD_G_EAS: 0.3165%
gnomAD_G_NFE: 0.1731%
gnomAD_G_SAS: 0.1366%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 3-195750391-AGGCCT-A [0/1] rs10564482
Variant score: 0.551
Transcripts:
MUC4:ENST00000463781.8:c.15871+493_15871+497del:p.(=)
Pathogenicity Data:
Best Score: 0.550845
REMM: 0.551
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 3-195782780-G-A [0/1] rs199497030
Variant score: 0.542
Transcripts:
MUC4:ENST00000463781.8:c.8800C>T:p.(Leu2934Phe)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_G_AFR: 0.5364%
gnomAD_G_AMR: 0.0415%
gnomAD_G_EAS: 0.1542%
gnomAD_G_NFE: 0.1246%
gnomAD_G_SAS: 0.0462%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 3-195762575-GGGCCCTGCACCGCCACGCACCC-G [0/1]
Variant score: 0.464
Transcripts:
MUC4:ENST00000463781.8:c.14344+258_14344+279del:p.(=)
Pathogenicity Data:
Best Score: 0.464285
REMM: 0.464
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195795851-G-T [0/1] rs71617322
Variant score: 0.434
Transcripts:
MUC4:ENST00000463781.8:c.83-4354C>A:p.(=)
Pathogenicity Data:
Best Score: 0.433843
REMM: 0.434
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195764309-C-T [0/1] rs2880893
Variant score: 0.426
Transcripts:
MUC4:ENST00000463781.8:c.13925-145G>A:p.(=)
Pathogenicity Data:
Best Score: 0.4323
REMM: 0.432
Frequency Data:
gnomAD_E_NFE: 0.0253%
gnomAD_E_SAS: 0.0087%
gnomAD_G_AFR: 0.0291%
gnomAD_G_AMR: 0.0494%
gnomAD_G_NFE: 0.1043%
MISSENSE_VARIANT SNV 3-195785726-G-A [0/1] rs6799339
Variant score: 0.381
Transcripts:
MUC4:ENST00000463781.8:c.5854C>T:p.(Pro1952Ser)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 1.3084%
gnomAD_E_AMR: 0.4195%
gnomAD_E_EAS: 0.3856%
gnomAD_E_NFE: 0.9207%
gnomAD_E_SAS: 0.5217%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195767615-C-T [0/1] rs1266417502
Variant score: 0.358
Transcripts:
MUC4:ENST00000463781.8:c.13530-864G>A:p.(=)
Pathogenicity Data:
Best Score: 0.358117
REMM: 0.358
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 3-195788137-C-G [0/1] rs201451131
Variant score: 0.354
Transcripts:
MUC4:ENST00000463781.8:c.3443G>C:p.(Gly1148Ala)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_G_AFR: 0.0703%
gnomAD_G_AMR: 0.2614%
gnomAD_G_EAS: 1.3932%
gnomAD_G_NFE: 0.7007%
gnomAD_G_SAS: 0.1344%
CODING_TRANSCRIPT_INTRON_VARIANT INS 3-195767621-T-TTGC [0/1] rs1553860755
Variant score: 0.353
Transcripts:
MUC4:ENST00000463781.8:c.13530-871_13530-870insGCA:p.(=)
Pathogenicity Data:
Best Score: 0.353225
REMM: 0.353
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195767616-C-T [0/1] rs1244770420
Variant score: 0.349
Transcripts:
MUC4:ENST00000463781.8:c.13530-865G>A:p.(=)
Pathogenicity Data:
Best Score: 0.348935
REMM: 0.349
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 3-195767557-ACCATTG-A [0/1] rs780062311
Variant score: 0.310
Transcripts:
MUC4:ENST00000463781.8:c.13530-812_13530-807del:p.(=)
Pathogenicity Data:
Best Score: 0.322383
REMM: 0.322
Frequency Data:
gnomAD_G_AMR: 0.2474%
gnomAD_G_NFE: 0.0581%
MISSENSE_VARIANT SNV 3-195779015-C-G [0/1] rs373784830
Variant score: 0.309
Transcripts:
MUC4:ENST00000463781.8:c.12565G>C:p.(Asp4189His)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_G_AFR: 1.5224%
gnomAD_G_AMR: 0.3788%
gnomAD_G_NFE: 0.5908%
gnomAD_G_SAS: 0.1698%
MISSENSE_VARIANT SNV 3-195779039-T-C [0/1] rs558861219
Variant score: 0.297
Transcripts:
MUC4:ENST00000463781.8:c.12541A>G:p.(Ser4181Gly)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_G_AFR: 1.5538%
gnomAD_G_AMR: 0.5656%
gnomAD_G_EAS: 0.4464%
gnomAD_G_NFE: 0.4039%
gnomAD_G_SAS: 0.4257%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195776411-A-G [0/1] rs1412554555
Variant score: 0.278
Transcripts:
MUC4:ENST00000463781.8:c.12943+1892T>C:p.(=)
Pathogenicity Data:
Best Score: 0.27754
REMM: 0.278
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777103-A-G [0/1] rs1466560030
Variant score: 0.269
Transcripts:
MUC4:ENST00000463781.8:c.12943+1200T>C:p.(=)
Pathogenicity Data:
Best Score: 0.269446
REMM: 0.269
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 3-195779074-A-G [0/1] rs200786826
Variant score: 0.268
Transcripts:
MUC4:ENST00000463781.8:c.12506T>C:p.(Val4169Ala)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 0.6099%
gnomAD_E_AMR: 0.5957%
gnomAD_E_EAS: 1.6262%
gnomAD_E_NFE: 0.2230%
gnomAD_E_SAS: 0.6634%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195776789-C-G [0/1]
Variant score: 0.264
Transcripts:
MUC4:ENST00000463781.8:c.12943+1514G>C:p.(=)
Pathogenicity Data:
Best Score: 0.263719
REMM: 0.264
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195776790-C-T [0/1]
Variant score: 0.263
Transcripts:
MUC4:ENST00000463781.8:c.12943+1513G>A:p.(=)
Pathogenicity Data:
Best Score: 0.263092
REMM: 0.263
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777347-T-A [1/1] rs111162726
Variant score: 0.256
Transcripts:
MUC4:ENST00000463781.8:c.12943+956A>T:p.(=)
Pathogenicity Data:
Best Score: 0.256174
REMM: 0.256
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195775649-G-C [0/1]
Variant score: 0.253
Transcripts:
MUC4:ENST00000463781.8:c.12944-1344C>G:p.(=)
Pathogenicity Data:
Best Score: 0.253406
REMM: 0.253
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195775681-G-C [1/1]
Variant score: 0.251
Transcripts:
MUC4:ENST00000463781.8:c.12944-1376C>G:p.(=)
Pathogenicity Data:
Best Score: 0.250802
REMM: 0.251
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777374-C-G [0/1]
Variant score: 0.249
Transcripts:
MUC4:ENST00000463781.8:c.12943+929G>C:p.(=)
Pathogenicity Data:
Best Score: 0.249479
REMM: 0.249
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777343-A-G [0/1] rs1360326464
Variant score: 0.247
Transcripts:
MUC4:ENST00000463781.8:c.12943+960T>C:p.(=)
Pathogenicity Data:
Best Score: 0.247346
REMM: 0.247
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195776489-T-C [0/1]
Variant score: 0.247
Transcripts:
MUC4:ENST00000463781.8:c.12943+1814A>G:p.(=)
Pathogenicity Data:
Best Score: 0.246723
REMM: 0.247
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777407-T-A [1/1]
Variant score: 0.246
Transcripts:
MUC4:ENST00000463781.8:c.12943+896A>T:p.(=)
Pathogenicity Data:
Best Score: 0.246499
REMM: 0.246
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777375-C-T [0/1]
Variant score: 0.245
Transcripts:
MUC4:ENST00000463781.8:c.12943+928G>A:p.(=)
Pathogenicity Data:
Best Score: 0.245112
REMM: 0.245
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777332-A-T [0/1]
Variant score: 0.245
Transcripts:
MUC4:ENST00000463781.8:c.12943+971T>A:p.(=)
Pathogenicity Data:
Best Score: 0.244652
REMM: 0.245
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195775650-T-C [0/1] rs1284581280
Variant score: 0.242
Transcripts:
MUC4:ENST00000463781.8:c.12944-1345A>G:p.(=)
Pathogenicity Data:
Best Score: 0.241869
REMM: 0.242
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777479-C-G [0/1]
Variant score: 0.241
Transcripts:
MUC4:ENST00000463781.8:c.12943+824G>C:p.(=)
Pathogenicity Data:
Best Score: 0.240962
REMM: 0.241
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777809-C-G [0/1]
Variant score: 0.238
Transcripts:
MUC4:ENST00000463781.8:c.12943+494G>C:p.(=)
Pathogenicity Data:
Best Score: 0.238379
REMM: 0.238
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195775588-A-G [0/1] rs373470710
Variant score: 0.238
Transcripts:
MUC4:ENST00000463781.8:c.12944-1283T>C:p.(=)
Pathogenicity Data:
Best Score: 0.246375
REMM: 0.246
Frequency Data:
gnomAD_G_AFR: 0.2176%
gnomAD_G_AMR: 0.0191%
gnomAD_G_NFE: 0.0153%
gnomAD_G_SAS: 0.0296%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195776426-A-G [0/1] rs375975016
Variant score: 0.229
Transcripts:
MUC4:ENST00000463781.8:c.12943+1877T>C:p.(=)
Pathogenicity Data:
Best Score: 0.23888
REMM: 0.239
Frequency Data:
gnomAD_G_NFE: 0.0145%
gnomAD_G_SAS: 0.2732%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777482-T-A [1/1]
Variant score: 0.217
Transcripts:
MUC4:ENST00000463781.8:c.12943+821A>T:p.(=)
Pathogenicity Data:
Best Score: 0.216927
REMM: 0.217
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195775813-G-A [0/1] rs563551133
Variant score: 0.212
Transcripts:
MUC4:ENST00000463781.8:c.12944-1508C>T:p.(=)
Pathogenicity Data:
Best Score: 0.229319
REMM: 0.229
Frequency Data:
gnomAD_G_AMR: 0.1608%
gnomAD_G_NFE: 0.0267%
gnomAD_G_SAS: 0.4505%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195776250-C-T [0/1] rs1462162391
Variant score: 0.203
Transcripts:
MUC4:ENST00000463781.8:c.12944-1945G>A:p.(=)
Pathogenicity Data:
Best Score: 0.202694
REMM: 0.203
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195776370-C-T [0/1]
Variant score: 0.201
Transcripts:
MUC4:ENST00000463781.8:c.12943+1933G>A:p.(=)
Pathogenicity Data:
Best Score: 0.200775
REMM: 0.201
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195776309-C-G [0/1]
Variant score: 0.179
Transcripts:
MUC4:ENST00000463781.8:c.12943+1994G>C:p.(=)
Pathogenicity Data:
Best Score: 0.178634
REMM: 0.179
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195776310-C-T [0/1] rs1244362407
Variant score: 0.177
Transcripts:
MUC4:ENST00000463781.8:c.12943+1993G>A:p.(=)
Pathogenicity Data:
Best Score: 0.177217
REMM: 0.177
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195776355-C-T [0/1] rs1358554519
Variant score: 0.162
Transcripts:
MUC4:ENST00000463781.8:c.12943+1948G>A:p.(=)
Pathogenicity Data:
Best Score: 0.16181
REMM: 0.162
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195776531-G-A [0/1]
Variant score: 0.160
Transcripts:
MUC4:ENST00000463781.8:c.12943+1772C>T:p.(=)
Pathogenicity Data:
Best Score: 0.159656
REMM: 0.160
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777779-C-G [0/1] rs374088007
Variant score: 0.158
Transcripts:
MUC4:ENST00000463781.8:c.12943+524G>C:p.(=)
Pathogenicity Data:
Best Score: 0.158556
REMM: 0.159
Frequency Data:
gnomAD_G_AFR: 0.0150%
gnomAD_G_NFE: 0.0114%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195776354-C-G [0/1]
Variant score: 0.155
Transcripts:
MUC4:ENST00000463781.8:c.12943+1949G>C:p.(=)
Pathogenicity Data:
Best Score: 0.154541
REMM: 0.155
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195776818-G-A [0/1] rs1403792613
Variant score: 0.151
Transcripts:
MUC4:ENST00000463781.8:c.12943+1485C>T:p.(=)
Pathogenicity Data:
Best Score: 0.151008
REMM: 0.151
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195776038-G-A [0/1] rs1490111840
Variant score: 0.144
Transcripts:
MUC4:ENST00000463781.8:c.12944-1733C>T:p.(=)
Pathogenicity Data:
Best Score: 0.14639
REMM: 0.146
Frequency Data:
gnomAD_G_AMR: 0.1310%
gnomAD_G_NFE: 0.0229%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777299-C-G [0|1]
Variant score: 0.136
Transcripts:
MUC4:ENST00000463781.8:c.12943+1004G>C:p.(=)
Pathogenicity Data:
Best Score: 0.136381
REMM: 0.136
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195776249-C-G [0/1]
Variant score: 0.136
Transcripts:
MUC4:ENST00000463781.8:c.12944-1944G>C:p.(=)
Pathogenicity Data:
Best Score: 0.135924
REMM: 0.136
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195775787-T-A [1/1] rs373122322
Variant score: 0.136
Transcripts:
MUC4:ENST00000463781.8:c.12944-1482A>T:p.(=)
Pathogenicity Data:
Best Score: 0.28361
REMM: 0.284
Frequency Data:
gnomAD_G_AFR: 0.2160%
gnomAD_G_AMR: 1.2539%
gnomAD_G_NFE: 1.1125%
gnomAD_G_SAS: 1.5789%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195776219-T-C [0/1]
Variant score: 0.134
Transcripts:
MUC4:ENST00000463781.8:c.12944-1914A>G:p.(=)
Pathogenicity Data:
Best Score: 0.134061
REMM: 0.134
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777150-C-T [1/1] rs1312279059
Variant score: 0.132
Transcripts:
MUC4:ENST00000463781.8:c.12943+1153G>A:p.(=)
Pathogenicity Data:
Best Score: 0.13202
REMM: 0.132
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195776369-G-C [0/1]
Variant score: 0.128
Transcripts:
MUC4:ENST00000463781.8:c.12943+1934C>G:p.(=)
Pathogenicity Data:
Best Score: 0.127665
REMM: 0.128
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777884-C-G [0/1] rs62282464
Variant score: 0.124
Transcripts:
MUC4:ENST00000463781.8:c.12943+419G>C:p.(=)
Pathogenicity Data:
Best Score: 0.125955
REMM: 0.126
Frequency Data:
gnomAD_G_AFR: 0.0809%
gnomAD_G_AMR: 0.0741%
gnomAD_G_NFE: 0.0841%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195776039-G-C [0/1] rs1422618162
Variant score: 0.124
Transcripts:
MUC4:ENST00000463781.8:c.12944-1734C>G:p.(=)
Pathogenicity Data:
Best Score: 0.124167
REMM: 0.124
Frequency Data:
gnomAD_G_AFR: 0.0249%
gnomAD_G_NFE: 0.0153%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195776999-T-C [0/1]
Variant score: 0.120
Transcripts:
MUC4:ENST00000463781.8:c.12943+1304A>G:p.(=)
Pathogenicity Data:
Best Score: 0.11995
REMM: 0.120
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195776999-T-G [0/1]
Variant score: 0.120
Transcripts:
MUC4:ENST00000463781.8:c.12943+1304A>C:p.(=)
Pathogenicity Data:
Best Score: 0.11995
REMM: 0.120
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195776561-G-A [0/1]
Variant score: 0.115
Transcripts:
MUC4:ENST00000463781.8:c.12943+1742C>T:p.(=)
Pathogenicity Data:
Best Score: 0.114971
REMM: 0.115
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777298-A-G [0|1] rs1376476134
Variant score: 0.112
Transcripts:
MUC4:ENST00000463781.8:c.12943+1005T>C:p.(=)
Pathogenicity Data:
Best Score: 0.149038
REMM: 0.149
Frequency Data:
gnomAD_G_AFR: 1.0417%
gnomAD_G_NFE: 0.9259%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195775545-T-C [0/1] rs867600869
Variant score: 0.100
Transcripts:
MUC4:ENST00000463781.8:c.12944-1240A>G:p.(=)
Pathogenicity Data:
Best Score: 0.102842
REMM: 0.103
Frequency Data:
gnomAD_G_AFR: 0.1825%
gnomAD_G_AMR: 0.0229%
gnomAD_G_EAS: 0.0760%
gnomAD_G_NFE: 0.0107%
SYNONYMOUS_VARIANT SNV 3-195779007-G-C [0/1]
Variant score: 0.100
Transcripts:
MUC4:ENST00000463781.8:c.12573C>G:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
SYNONYMOUS_VARIANT SNV 3-195779025-T-C [0/1]
Variant score: 0.100
Transcripts:
MUC4:ENST00000463781.8:c.12555A>G:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
SYNONYMOUS_VARIANT SNV 3-195787857-T-A [0/1] rs530253873
ClinVar: BENIGN (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.100
Transcripts:
MUC4:ENST00000463781.8:c.3723A>T:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777284-T-C [0/1]
Variant score: 0.098
Transcripts:
MUC4:ENST00000463781.8:c.12943+1019A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0979187
REMM: 0.098
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777810-C-T [0/1] rs1158332280
Variant score: 0.096
Transcripts:
MUC4:ENST00000463781.8:c.12943+493G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0960623
REMM: 0.096
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777689-T-C [0/1]
Variant score: 0.093
Transcripts:
MUC4:ENST00000463781.8:c.12943+614A>G:p.(=)
Pathogenicity Data:
Best Score: 0.092598
REMM: 0.093
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195767737-C-T [1/1] rs1025427994
Variant score: 0.090
Transcripts:
MUC4:ENST00000463781.8:c.13530-986G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0952405
REMM: 0.095
Frequency Data:
gnomAD_G_AFR: 0.3378%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195775529-C-G [0/1] rs867298548
Variant score: 0.089
Transcripts:
MUC4:ENST00000463781.8:c.12944-1224G>C:p.(=)
Pathogenicity Data:
Best Score: 0.0893643
REMM: 0.089
Frequency Data:
gnomAD_G_NFE: 0.0113%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195775528-A-G [0/1] rs375777105
Variant score: 0.087
Transcripts:
MUC4:ENST00000463781.8:c.12944-1223T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0883643
REMM: 0.088
Frequency Data:
gnomAD_G_AFR: 0.0715%
gnomAD_G_NFE: 0.0131%
gnomAD_G_SAS: 0.0724%
SYNONYMOUS_VARIANT SNV 3-195780900-C-T [0/1] rs200652820
Variant score: 0.084
Transcripts:
MUC4:ENST00000463781.8:c.10680G>A:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_G_AFR: 0.7623%
gnomAD_G_AMR: 0.7884%
gnomAD_G_EAS: 0.3937%
gnomAD_G_NFE: 0.3736%
gnomAD_G_SAS: 0.4371%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195775544-G-C [0/1] rs867250483
Variant score: 0.082
Transcripts:
MUC4:ENST00000463781.8:c.12944-1239C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0826163
REMM: 0.083
Frequency Data:
gnomAD_G_AFR: 0.0719%
gnomAD_G_AMR: 0.0188%
gnomAD_G_EAS: 0.0909%
gnomAD_G_NFE: 0.0096%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777149-T-G [1/1]
Variant score: 0.080
Transcripts:
MUC4:ENST00000463781.8:c.12943+1154A>C:p.(=)
Pathogenicity Data:
Best Score: 0.0803881
REMM: 0.080
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777645-T-C [0/1] rs377185558
Variant score: 0.079
Transcripts:
MUC4:ENST00000463781.8:c.12943+658A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0793302
REMM: 0.079
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777644-G-C [0/1]
Variant score: 0.078
Transcripts:
MUC4:ENST00000463781.8:c.12943+659C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0775647
REMM: 0.078
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777840-C-T [0/1]
Variant score: 0.071
Transcripts:
MUC4:ENST00000463781.8:c.12943+463G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0708008
REMM: 0.071
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777105-T-C [0/1] rs866043049
Variant score: 0.070
Transcripts:
MUC4:ENST00000463781.8:c.12943+1198A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0703024
REMM: 0.070
Frequency Data:
No frequency data
SYNONYMOUS_VARIANT SNV 3-195785697-T-C [0/1] rs199625793
Variant score: 0.070
Transcripts:
MUC4:ENST00000463781.8:c.5883A>G:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 1.1628%
gnomAD_E_AMR: 0.1817%
gnomAD_E_EAS: 0.2906%
gnomAD_E_NFE: 0.1190%
gnomAD_E_SAS: 0.3079%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777839-T-C [0/1]
Variant score: 0.070
Transcripts:
MUC4:ENST00000463781.8:c.12943+464A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0699437
REMM: 0.070
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195777885-C-T [0/1] rs770035281
Variant score: 0.064
Transcripts:
MUC4:ENST00000463781.8:c.12943+418G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0647214
REMM: 0.065
Frequency Data:
gnomAD_G_AFR: 0.0604%
gnomAD_G_AMR: 0.0526%
gnomAD_G_NFE: 0.0400%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195767528-T-C [0/1]
Variant score: 0.054
Transcripts:
MUC4:ENST00000463781.8:c.13530-777A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0542425
REMM: 0.054
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195767530-G-A [0/1] rs148745721
Variant score: 0.037
Transcripts:
MUC4:ENST00000463781.8:c.13530-779C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0572111
REMM: 0.057
Frequency Data:
gnomAD_G_AFR: 0.5084%
gnomAD_G_AMR: 0.7123%
gnomAD_G_EAS: 1.2953%
gnomAD_G_NFE: 0.8573%
gnomAD_G_SAS: 0.2817%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195773678-C-T [0/1] rs2550250
Variant score: 0.028
Transcripts:
MUC4:ENST00000463781.8:c.13077+494G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0288421
REMM: 0.029
Frequency Data:
gnomAD_G_AFR: 0.0087%
gnomAD_G_AMR: 0.0791%
gnomAD_G_NFE: 0.1004%
gnomAD_G_SAS: 0.2560%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195767610-T-C [0/1] rs980952144
Variant score: 0.028
Transcripts:
MUC4:ENST00000463781.8:c.13530-859A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0433909
REMM: 0.043
Frequency Data:
gnomAD_G_AFR: 0.6833%
gnomAD_G_AMR: 0.7307%
gnomAD_G_EAS: 0.9434%
gnomAD_G_NFE: 1.3026%
gnomAD_G_SAS: 0.6536%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195773676-G-T [0/1] rs2550249
Variant score: 0.024
Transcripts:
MUC4:ENST00000463781.8:c.13077+496C>A:p.(=)
Pathogenicity Data:
Best Score: 0.0256024
REMM: 0.026
Frequency Data:
gnomAD_G_AFR: 0.0257%
gnomAD_G_AMR: 0.0730%
gnomAD_G_NFE: 0.1601%
gnomAD_G_SAS: 0.3191%
DOWNSTREAM_GENE_VARIANT SNV 3-195744050-G-A [0/1] rs377045820
Variant score: 0.015
Transcripts:
MUC4:ENST00000463781.8::
Pathogenicity Data:
Best Score: 0.019956
REMM: 0.020
Frequency Data:
UK10K: 0.8596%
gnomAD_G_AFR: 0.1646%
gnomAD_G_AMR: 0.4799%
gnomAD_G_EAS: 0.0387%
gnomAD_G_NFE: 0.9185%
gnomAD_G_SAS: 1.0447%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195750472-C-T [0/1] rs2880894
Variant score: 0.014
Transcripts:
MUC4:ENST00000463781.8:c.15871+417G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0141028
REMM: 0.014
Frequency Data:
gnomAD_E_AFR: 0.1457%
gnomAD_E_EAS: 0.0796%
gnomAD_E_NFE: 0.0790%
gnomAD_G_AFR: 0.1168%
gnomAD_G_AMR: 0.0417%
gnomAD_G_EAS: 0.0216%
gnomAD_G_NFE: 0.0259%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195749685-G-C [0/1] rs79750874
Variant score: 0.001
Transcripts:
MUC4:ENST00000463781.8:c.15872-621C>G:p.(=)
Pathogenicity Data:
Best Score: 0.00145952
REMM: 0.001
Frequency Data:
No frequency data
DOWNSTREAM_GENE_VARIANT SNV 3-195746636-A-T [0/1] rs148502792
Variant score: 0.001
Transcripts:
MUC4:ENST00000463781.8::
Pathogenicity Data:
Best Score: 0.00415238
REMM: 0.004
Frequency Data:
gnomAD_E_AMR: 0.4425%
gnomAD_E_NFE: 0.7164%
gnomAD_E_SAS: 1.8131%
gnomAD_G_AFR: 0.0842%
gnomAD_G_AMR: 0.3859%
gnomAD_G_NFE: 0.7079%
gnomAD_G_SAS: 1.2666%
CODING_TRANSCRIPT_INTRON_VARIANT INS 3-195750125-G-GGT [0|1] rs570908962
Variant score: 0.001
Transcripts:
MUC4:ENST00000463781.8:c.15871+763_15871+764insAC:p.(=)
Pathogenicity Data:
Best Score: 0.00114286
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-195758569-A-G [0|1] rs3103933
Variant score: 0.000
Transcripts:
MUC4:ENST00000463781.8:c.14986+555T>C:p.(=)
Pathogenicity Data:
Best Score: 1.42857E-4
REMM: 0.000
Frequency Data:
No frequency data

TRPS1

Exomiser Score: 0.710 (p=2.1E-2)

Phenotype Score: 0.501

Variant Score: 0.977

Phenotype matches:
Phenotypic similarity 0.465 to Trichorhinophalangeal syndrome type 1 associated with TRPS1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000768, Pectus carinatum
HP:0006625, Multifocal breast carcinoma - HP:0000768, Pectus carinatum
Phenotypic similarity 0.380 to mouse mutant involving TRPS1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0010103, small thoracic cage
HP:0006625, Multifocal breast carcinoma - MP:0010103, small thoracic cage
Proximity score 0.501 in interactome to SOX9 and phenotypic similarity 0.614 to 46,XY partial gonadal dysgenesis associated with SOX9.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Proximity score 0.501 in interactome to SOX9 and phenotypic similarity 0.353 to mouse mutant of SOX9.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0010103, small thoracic cage
HP:0006625, Multifocal breast carcinoma - MP:0010103, small thoracic cage
Proximity score 0.501 in interactome to SOX9 and phenotypic similarity 0.265 to fish mutant of SOX9.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0000138, chondrocyte disorganized, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0000138, chondrocyte disorganized, abnormal
Known diseases:
OMIM:190350 Trichorhinophalangeal syndrome, type I - autosomal dominant
OMIM:190351 Trichorhinophalangeal syndrome, type III - autosomal dominant
ORPHA:502 Trichorhinophalangeal syndrome type 2 (CNV)
ORPHA:77258 Trichorhinophalangeal syndrome type 1 - autosomal dominant
ORPHA:77258 Trichorhinophalangeal syndrome type 1 - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.710 (p=2.1E-2)

Phenotype Score: 0.501

Variant Score: 0.977

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.465 to ORPHA:77258 Trichorhinophalangeal syndrome type 1
Phenotypic similarity 0.453 to OMIM:190350 Trichorhinophalangeal syndrome, type I
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-115482637-T-G [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.977 CONTRIBUTING VARIANT
Transcripts:
TRPS1:ENST00000395715.8:c.2701-64185A>C:p.(=)
Pathogenicity Data:
Best Score: 0.976864
REMM: 0.977
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.044 (p=3.4E-1)

Phenotype Score: 0.251

Variant Score: 0.827

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-115482637-T-G [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.977 CONTRIBUTING VARIANT
Transcripts:
TRPS1:ENST00000395715.8:c.2701-64185A>C:p.(=)
Pathogenicity Data:
Best Score: 0.976864
REMM: 0.977
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-115459628-C-A [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.678 CONTRIBUTING VARIANT
Transcripts:
TRPS1:ENST00000395715.8:c.2701-41176G>T:p.(=)
Pathogenicity Data:
Best Score: 0.677898
REMM: 0.678
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-115578054-T-A [0|1]
Variant score: 0.653
Transcripts:
TRPS1:ENST00000395715.8:c.2700+8947A>T:p.(=)
Pathogenicity Data:
Best Score: 0.652529
REMM: 0.653
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 8-115638970-G-A [0/1] rs533502510
Variant score: 0.569
Transcripts:
TRPS1:ENST00000395715.8:c.-121-15212C>T:p.(=)
Pathogenicity Data:
Best Score: 0.585762
REMM: 0.586
Frequency Data:
gnomAD_G_AFR: 0.1950%
gnomAD_G_NFE: 0.0015%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-115476011-T-G [1/1] rs79113791
Variant score: 0.405
Transcripts:
TRPS1:ENST00000395715.8:c.2701-57559A>C:p.(=)
Pathogenicity Data:
Best Score: 0.404798
REMM: 0.405
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-115495688-T-TA [0/1] rs3839860
Variant score: 0.390
Transcripts:
TRPS1:ENST00000395715.8:c.2701-77237_2701-77236insT:p.(=)
Pathogenicity Data:
Best Score: 0.393139
REMM: 0.393
Frequency Data:
gnomAD_G_AFR: 0.0321%
gnomAD_G_AMR: 0.0136%
gnomAD_G_EAS: 0.0397%
gnomAD_G_NFE: 0.0508%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-115576286-T-G [0/1] rs201488903
Variant score: 0.286
Transcripts:
TRPS1:ENST00000395715.8:c.2700+10715A>C:p.(=)
Pathogenicity Data:
Best Score: 0.701848
REMM: 0.702
Frequency Data:
gnomAD_G_AFR: 0.3590%
gnomAD_G_AMR: 0.3058%
gnomAD_G_EAS: 1.6819%
gnomAD_G_NFE: 0.6205%
gnomAD_G_SAS: 0.7918%
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-115535236-C-CATATATAGCAT [0/1]
Variant score: 0.251
Transcripts:
TRPS1:ENST00000395715.8:c.2700+51764_2700+51765insATGCTATATAT:p.(=)
Pathogenicity Data:
Best Score: 0.250861
REMM: 0.251
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-115535293-T-TAGCATATATATAGCATATATAGCATATATATAGCATATATATAGCATATATAG [0/1]
Variant score: 0.106
Transcripts:
TRPS1:ENST00000395715.8:c.2700+51707_2700+51708insCTATATATGCTATATATATGCTATATATATGCTATATATGCTATATATATGCT:p.(=)
Pathogenicity Data:
Best Score: 0.106013
REMM: 0.106
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-115533460-C-T [1/1]
Variant score: 0.079
Transcripts:
TRPS1:ENST00000395715.8:c.2700+53541G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0786623
REMM: 0.079
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT INS 8-115626287-G-GA [0/1] rs143761397
Variant score: 0.061
Transcripts:
TRPS1:ENST00000395715.8:c.-121-2530_-121-2529insT:p.(=)
Pathogenicity Data:
Best Score: 0.0971476
REMM: 0.097
Frequency Data:
gnomAD_G_AFR: 0.2349%
gnomAD_G_AMR: 0.5694%
gnomAD_G_EAS: 0.1061%
gnomAD_G_NFE: 0.9579%
gnomAD_G_SAS: 1.3207%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-115424108-T-C [0/1] rs557254522
Variant score: 0.041
Transcripts:
TRPS1:ENST00000395715.8:c.2701-5656A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0410778
REMM: 0.041
Frequency Data:
UK10K: 0.0264%
gnomAD_G_AFR: 0.0096%
gnomAD_G_NFE: 0.0412%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-115524319-CT-C [0/1]
Variant score: 0.016
Transcripts:
TRPS1:ENST00000395715.8:c.2700+62681del:p.(=)
Pathogenicity Data:
Best Score: 0.015825
REMM: 0.016
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-115583601-C-G [0/1] rs117426022
Variant score: 0.010
Transcripts:
TRPS1:ENST00000395715.8:c.2700+3400G>C:p.(=)
Pathogenicity Data:
Best Score: 0.0108345
REMM: 0.011
Frequency Data:
UK10K: 0.4628%
gnomAD_G_AFR: 0.0818%
gnomAD_G_AMR: 0.1831%
gnomAD_G_EAS: 0.0386%
gnomAD_G_NFE: 0.5138%
gnomAD_G_SAS: 0.3526%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-115578055-C-G [0|1]
Variant score: 0.006
Transcripts:
TRPS1:ENST00000395715.8:c.2700+8946G>C:p.(=)
Pathogenicity Data:
Best Score: 0.00553095
REMM: 0.006
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-115476007-T-A [1/1] rs12545220
Variant score: 0.000
Transcripts:
TRPS1:ENST00000395715.8:c.2701-57555A>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data

CDH1

Exomiser Score: 0.669 (p=3.6E-2)

Phenotype Score: 0.998

Variant Score: 0.394

Phenotype matches:
Phenotypic similarity 0.998 to Breast cancer, lobular, somatic associated with CDH1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Phenotypic similarity 0.292 to zebrafish mutant involving CDH1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0001556, notochord kinked, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0001556, notochord kinked, abnormal
Proximity score 0.525 in interactome to EPCAM and phenotypic similarity 0.998 to Lynch syndrome associated with EPCAM.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Known diseases:
OMIM:114480 Breast cancer, lobular, somatic - autosomal dominant
OMIM:119580 Blepharocheilodontic syndrome 1 - autosomal dominant
OMIM:137215 Diffuse gastric and lobular breast cancer syndrome with or without cleft lip and/or palate - autosomal dominant
OMIM:167000 Ovarian cancer, somatic - autosomal dominant
OMIM:176807 Prostate cancer, susceptibility to (susceptibility)
OMIM:608089 Endometrial carcinoma, somatic - autosomal dominant
ORPHA:199306 Cleft lip/palate (susceptibility)
ORPHA:1997 Blepharo-cheilo-odontic syndrome - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.669 (p=3.6E-2)

Phenotype Score: 0.998

Variant Score: 0.394

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.998 to OMIM:114480 Breast cancer, lobular, somatic
Phenotypic similarity 0.998 to OMIM:167000 Ovarian cancer, somatic
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 16-68831069-CT-C [0/1] rs1157074539
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting, PP4]
Variant score: 0.394 CONTRIBUTING VARIANT
Transcripts:
CDH1:ENST00000261769.10:c.2439+1273del:p.(=)
Pathogenicity Data:
Best Score: 0.394413
REMM: 0.394
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.009 (p=4.8E-1)

Phenotype Score: 0.263

Variant Score: 0.637

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 16-68762912-CAAAAAAAAAA-C [1/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.637 CONTRIBUTING VARIANT
Transcripts:
CDH1:ENST00000261769.10:c.163+24502_163+24511del:p.(=)
Pathogenicity Data:
Best Score: 0.637124
REMM: 0.637
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 16-68762371-G-A [0/1] rs145599669
Variant score: 0.785
Transcripts:
CDH1:ENST00000261769.10:c.163+23960G>A:p.(=)
Pathogenicity Data:
Best Score: 0.9068
REMM: 0.907
Frequency Data:
UK10K: 0.6876%
gnomAD_G_AFR: 0.1275%
gnomAD_G_AMR: 0.1504%
gnomAD_G_NFE: 0.5204%
CODING_TRANSCRIPT_INTRON_VARIANT INS 16-68755282-C-CAAAAAAAA [1/1]
Variant score: 0.603
Transcripts:
CDH1:ENST00000261769.10:c.163+16871_163+16872insAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.603343
REMM: 0.603
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 16-68786534-C-CTTTTTTTT [1/1] rs3074434
Variant score: 0.493
Transcripts:
CDH1:ENST00000261769.10:c.164-15136_164-15135insTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.493445
REMM: 0.493
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 16-68738964-T-TTTTTA [1/1]
Variant score: 0.459
Transcripts:
CDH1:ENST00000261769.10:c.163+553_163+554insTTTTA:p.(=)
Pathogenicity Data:
Best Score: 0.45873
REMM: 0.459
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 16-68731461-CAT-C [1|1]
Variant score: 0.117
Transcripts:
CDH1:ENST00000261769.10::
Pathogenicity Data:
Best Score: 0.117028
REMM: 0.117
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 16-68731413-TAC-T [1|1] rs1555509194
Variant score: 0.066
Transcripts:
CDH1:ENST00000261769.10::
Pathogenicity Data:
Best Score: 0.116691
REMM: 0.117
Frequency Data:
gnomAD_G_AFR: 1.3190%
gnomAD_G_AMR: 0.7263%
gnomAD_G_EAS: 0.3893%
gnomAD_G_NFE: 1.4355%
gnomAD_G_SAS: 0.3769%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 16-68771925-G-A [0/1] rs144153395
Variant score: 0.052
Transcripts:
CDH1:ENST00000261769.10:c.164-29745G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0605111
REMM: 0.061
Frequency Data:
UK10K: 0.7009%
gnomAD_G_AFR: 0.1277%
gnomAD_G_AMR: 0.1504%
gnomAD_G_NFE: 0.5205%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 16-68821840-G-A [0/1] rs150483419
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.039
Transcripts:
CDH1:ENST00000261769.10:c.1712-161G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0465798
REMM: 0.047
Frequency Data:
UK10K: 0.7538%
gnomAD_G_AFR: 0.0770%
gnomAD_G_AMR: 0.6018%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.7368%
gnomAD_G_SAS: 0.0622%
CODING_TRANSCRIPT_INTRON_VARIANT INS 16-68750150-C-CTTTTTTTTTTTTTTTT [1/1]
Variant score: 0.036
Transcripts:
CDH1:ENST00000261769.10:c.163+11739_163+11740insTTTTTTTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.036431
REMM: 0.036
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 16-68739608-AT-A [0/1] rs549473582
Variant score: 0.033
Transcripts:
CDH1:ENST00000261769.10:c.163+1198del:p.(=)
Pathogenicity Data:
Best Score: 0.0325687
REMM: 0.033
Frequency Data:
No frequency data
INTERGENIC_VARIANT INS 16-68731042-A-AT [0/1]
Variant score: 0.014
Transcripts:
CDH1:ENST00000261769.10::
Pathogenicity Data:
Best Score: 0.0136262
REMM: 0.014
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 16-68731045-A-T [1/1]
Variant score: 0.013
Transcripts:
CDH1:ENST00000261769.10::
Pathogenicity Data:
Best Score: 0.0134512
REMM: 0.013
Frequency Data:
No frequency data
DOWNSTREAM_GENE_VARIANT DEL 16-68837085-CT-C [1/1] rs35409928
Variant score: 0.013
Transcripts:
CDH1:ENST00000261769.10::
Pathogenicity Data:
Best Score: 0.0132083
REMM: 0.013
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 16-68731043-A-T [0/1] rs1441958854
Variant score: 0.013
Transcripts:
CDH1:ENST00000261769.10::
Pathogenicity Data:
Best Score: 0.0127012
REMM: 0.013
Frequency Data:
No frequency data
INTERGENIC_VARIANT INS 16-68731043-A-ATATAT [0/1]
Variant score: 0.013
Transcripts:
CDH1:ENST00000261769.10::
Pathogenicity Data:
Best Score: 0.0127012
REMM: 0.013
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 16-68758207-CT-C [1/1] rs57413297
Variant score: 0.003
Transcripts:
CDH1:ENST00000261769.10:c.163+19797del:p.(=)
Pathogenicity Data:
Best Score: 0.00288889
REMM: 0.003
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 16-68819181-G-T [0/1] rs142906029
Variant score: 0.002
Transcripts:
CDH1:ENST00000261769.10:c.1566-99G>T:p.(=)
Pathogenicity Data:
Best Score: 0.00244444
REMM: 0.002
Frequency Data:
UK10K: 0.2909%
gnomAD_E_AFR: 0.0313%
gnomAD_E_AMR: 0.1450%
gnomAD_E_EAS: 0.0052%
gnomAD_E_NFE: 0.3116%
gnomAD_E_SAS: 0.0112%
gnomAD_G_AFR: 0.0361%
gnomAD_G_AMR: 0.3206%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.3602%
gnomAD_G_SAS: 0.0415%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 16-68771708-C-T [0/1] rs148437378
Variant score: 0.000
Transcripts:
CDH1:ENST00000261769.10:c.164-29962C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0268%
gnomAD_G_AMR: 0.0928%
gnomAD_G_NFE: 0.2565%
gnomAD_G_SAS: 0.1675%

ATP5F1A

Exomiser Score: 0.659 (p=3.9E-2)

Phenotype Score: 0.503

Variant Score: 0.950

Phenotype matches:
Proximity score 0.503 in interactome to SDHB and phenotypic similarity 0.904 to Cowden syndrome associated with SDHB.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Known diseases:
OMIM:615228 ?Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4B, encephalopathic type (unconfirmed)
OMIM:616045 ?Combined oxidative phosphorylation deficiency 22 (unconfirmed)
OMIM:620358 Mitochondrial complex V (ATP synthase) deficiency, nuclear type 4A - autosomal dominant
ORPHA:254913 Isolated ATP synthase deficiency - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.659 (p=3.9E-2)

Phenotype Score: 0.503

Variant Score: 0.950

No phenotype matches to diseases with this MOI.
Variants contributing to score:
UPSTREAM_GENE_VARIANT DEL 18-46098362-ACC-A [1|1] rs143002048
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.950 CONTRIBUTING VARIANT
Transcripts:
ATP5F1A:ENST00000398752.11::
Pathogenicity Data:
Best Score: 0.949694
REMM: 0.950
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.328 (p=1.5E-1)

Phenotype Score: 0.503

Variant Score: 0.800

No phenotype matches to diseases with this MOI.
Variants contributing to score:
SPLICE_REGION_VARIANT SNV 18-46087003-A-C [0/1] rs760107868
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:1, LB:2)
Variant score: 0.800 CONTRIBUTING VARIANT
Transcripts:
ATP5F1A:ENST00000398752.11:c.1176+5T>G:p.?
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_NFE: 0.0011%
gnomAD_E_SAS: 0.0012%
gnomAD_G_NFE: 0.0015%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT INS 18-46096500-C-CAAAAAAA [1/1]
Variant score: 0.789
Transcripts:
ATP5F1A:ENST00000398752.11:c.61-1370_61-1369insTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.78861
REMM: 0.789
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT SNV 18-46098370-T-C [1|1]
Variant score: 0.546
Transcripts:
ATP5F1A:ENST00000398752.11::
Pathogenicity Data:
Best Score: 0.54604
REMM: 0.546
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT SNV 18-46098368-T-C [1|1]
Variant score: 0.528
Transcripts:
ATP5F1A:ENST00000398752.11::
Pathogenicity Data:
Best Score: 0.528214
REMM: 0.528
Frequency Data:
No frequency data
THREE_PRIME_UTR_EXON_VARIANT DEL 18-46081696-AAC-A [1|0]
Variant score: 0.376
Transcripts:
ATP5F1A:ENST00000398752.11:c.*2584_*2585del:p.(=)
Pathogenicity Data:
Best Score: 0.375988
REMM: 0.376
Frequency Data:
No frequency data
THREE_PRIME_UTR_EXON_VARIANT INS 18-46081669-A-AAAC [1|0] rs1568240622
Variant score: 0.264
Transcripts:
ATP5F1A:ENST00000398752.11:c.*2612_*2613insGTT:p.(=)
Pathogenicity Data:
Best Score: 0.264692
REMM: 0.265
Frequency Data:
gnomAD_G_NFE: 0.0097%
THREE_PRIME_UTR_EXON_VARIANT SNV 18-46081680-A-C [1|0] rs1207012212
Variant score: 0.192
Transcripts:
ATP5F1A:ENST00000398752.11:c.*2602T>G:p.(=)
Pathogenicity Data:
Best Score: 0.194634
REMM: 0.195
Frequency Data:
gnomAD_G_AFR: 0.0386%
gnomAD_G_AMR: 0.0548%
gnomAD_G_EAS: 0.1049%
gnomAD_G_NFE: 0.0712%

RELN

Exomiser Score: 0.634 (p=4.8E-2)

Phenotype Score: 0.502

Variant Score: 0.939

Phenotype matches:
Proximity score 0.502 in interactome to ITGA3 and phenotypic similarity 0.603 to Epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome associated with ITGA3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Known diseases:
OMIM:257320 Lissencephaly 2 (Norman-Roberts type) - autosomal recessive
OMIM:616436 Epilepsy, familial temporal lobe, 7 (susceptibility)
ORPHA:101046 Autosomal dominant epilepsy with auditory features - autosomal dominant
ORPHA:89844 Lissencephaly syndrome, Norman-Roberts type - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.634 (p=4.8E-2)

Phenotype Score: 0.502

Variant Score: 0.939

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103875758-T-A [0/1] rs911621909
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.939 CONTRIBUTING VARIANT
Transcripts:
RELN:ENST00000428762.6:c.337+41317A>T:p.(=)
Pathogenicity Data:
Best Score: 0.944481
REMM: 0.944
Frequency Data:
gnomAD_G_NFE: 0.0132%
gnomAD_G_SAS: 0.0414%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.534 (p=7.9E-2)

Phenotype Score: 0.502

Variant Score: 0.894

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103875758-T-A [0/1] rs911621909
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.939 CONTRIBUTING VARIANT
Transcripts:
RELN:ENST00000428762.6:c.337+41317A>T:p.(=)
Pathogenicity Data:
Best Score: 0.944481
REMM: 0.944
Frequency Data:
gnomAD_G_NFE: 0.0132%
gnomAD_G_SAS: 0.0414%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103699883-T-A [0/1] rs1834055361
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.849 CONTRIBUTING VARIANT
Transcripts:
RELN:ENST00000428762.6:c.902+1027A>T:p.(=)
Pathogenicity Data:
Best Score: 0.848768
REMM: 0.849
Frequency Data:
gnomAD_G_NFE: 0.0015%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103730536-C-T [0/1] rs548050854
Variant score: 0.660
Transcripts:
RELN:ENST00000428762.6:c.657-2329G>A:p.(=)
Pathogenicity Data:
Best Score: 0.665792
REMM: 0.666
Frequency Data:
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0066%
gnomAD_G_NFE: 0.0132%
gnomAD_G_SAS: 0.0623%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-103520957-AT-A [0/1]
Variant score: 0.548
Transcripts:
RELN:ENST00000428762.6:c.7668+1064del:p.(=)
Pathogenicity Data:
Best Score: 0.547645
REMM: 0.548
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-103983863-C-CTGTG [0/1] rs59702742
Variant score: 0.517
Transcripts:
RELN:ENST00000428762.6:c.226+5267_226+5268insCACA:p.(=)
Pathogenicity Data:
Best Score: 0.69416
REMM: 0.694
Frequency Data:
gnomAD_G_AFR: 0.7588%
gnomAD_G_AMR: 1.0611%
gnomAD_G_EAS: 0.1180%
gnomAD_G_NFE: 0.9141%
gnomAD_G_SAS: 0.7306%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103699825-A-G [0/1] rs1834054201
Variant score: 0.506
Transcripts:
RELN:ENST00000428762.6:c.902+1085T>C:p.(=)
Pathogenicity Data:
Best Score: 0.506583
REMM: 0.507
Frequency Data:
gnomAD_G_NFE: 0.0015%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103816261-C-A [0/1] rs140392759
Variant score: 0.476
Transcripts:
RELN:ENST00000428762.6:c.473+17276G>T:p.(=)
Pathogenicity Data:
Best Score: 0.653196
REMM: 0.653
Frequency Data:
UK10K: 0.8331%
gnomAD_G_AFR: 0.1926%
gnomAD_G_AMR: 1.0996%
gnomAD_G_NFE: 0.9307%
gnomAD_G_SAS: 0.4353%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-103773100-TTTTCTTTCTTTCTTTC-T [0/1]
Variant score: 0.354
Transcripts:
RELN:ENST00000428762.6:c.544+3441_544+3456del:p.(=)
Pathogenicity Data:
Best Score: 0.353932
REMM: 0.354
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-103485229-CA-C [1/1]
Variant score: 0.350
Transcripts:
RELN:ENST00000428762.6:c.9983+967del:p.(=)
Pathogenicity Data:
Best Score: 0.349819
REMM: 0.350
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-103544220-CTTTTTTTTTTTTTT-C [0/1] rs71154356
Variant score: 0.347
Transcripts:
RELN:ENST00000428762.6:c.6523+890_6523+903del:p.(=)
Pathogenicity Data:
Best Score: 0.346577
REMM: 0.347
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103822782-C-T [0/1]
Variant score: 0.317
Transcripts:
RELN:ENST00000428762.6:c.473+10755G>A:p.(=)
Pathogenicity Data:
Best Score: 0.317494
REMM: 0.317
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103800054-G-A [0|1] rs570689702
Variant score: 0.308
Transcripts:
RELN:ENST00000428762.6:c.474-23427C>T:p.(=)
Pathogenicity Data:
Best Score: 0.372779
REMM: 0.373
Frequency Data:
gnomAD_G_AFR: 0.1276%
gnomAD_G_AMR: 0.8244%
gnomAD_G_NFE: 0.6909%
gnomAD_G_SAS: 0.4353%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-103838208-CA-C [0/1]
Variant score: 0.242
Transcripts:
RELN:ENST00000428762.6:c.338-4537del:p.(=)
Pathogenicity Data:
Best Score: 0.242474
REMM: 0.242
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-103838208-CAA-C [0/1]
Variant score: 0.242
Transcripts:
RELN:ENST00000428762.6:c.338-4538_338-4537del:p.(=)
Pathogenicity Data:
Best Score: 0.242474
REMM: 0.242
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103746358-C-T [0/1] rs1216161945
Variant score: 0.171
Transcripts:
RELN:ENST00000428762.6:c.656+3068G>A:p.(=)
Pathogenicity Data:
Best Score: 0.170845
REMM: 0.171
Frequency Data:
gnomAD_G_NFE: 0.0118%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-103796894-AG-A [0/1]
Variant score: 0.127
Transcripts:
RELN:ENST00000428762.6:c.474-20268del:p.(=)
Pathogenicity Data:
Best Score: 0.126785
REMM: 0.127
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103717987-G-T [0/1]
Variant score: 0.125
Transcripts:
RELN:ENST00000428762.6:c.805+5153C>A:p.(=)
Pathogenicity Data:
Best Score: 0.125399
REMM: 0.125
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-103491846-T-TCACA [0|1] rs1381747766
Variant score: 0.091
Transcripts:
RELN:ENST00000428762.6:c.9443+106_9443+107insTGTG:p.(=)
Pathogenicity Data:
Best Score: 0.126074
REMM: 0.126
Frequency Data:
gnomAD_E_AFR: 0.0162%
gnomAD_E_EAS: 0.0718%
gnomAD_E_NFE: 0.0063%
gnomAD_E_SAS: 0.1681%
gnomAD_G_AFR: 0.1484%
gnomAD_G_AMR: 0.0349%
gnomAD_G_EAS: 0.1463%
gnomAD_G_NFE: 0.0303%
gnomAD_G_SAS: 1.1084%
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-103907414-G-GAAAAA [0/1]
Variant score: 0.049
Transcripts:
RELN:ENST00000428762.6:c.337+9660_337+9661insTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.0485984
REMM: 0.049
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103872547-G-A [0/1] rs75523556
Variant score: 0.033
Transcripts:
RELN:ENST00000428762.6:c.338-38875C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0420226
REMM: 0.042
Frequency Data:
gnomAD_G_AFR: 0.1391%
gnomAD_G_AMR: 0.2506%
gnomAD_G_EAS: 0.9607%
gnomAD_G_NFE: 0.1225%
gnomAD_G_SAS: 0.4106%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103872563-A-C [0/1] rs550058263
Variant score: 0.031
Transcripts:
RELN:ENST00000428762.6:c.338-38891T>G:p.(=)
Pathogenicity Data:
Best Score: 0.0310528
REMM: 0.031
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103911875-A-G [1/1] rs371270617
Variant score: 0.027
Transcripts:
RELN:ENST00000428762.6:c.337+5200T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0268817
REMM: 0.027
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-103907414-G-GAAAAAAAA [0/1] rs1795234328
Variant score: 0.019
Transcripts:
RELN:ENST00000428762.6:c.337+9660_337+9661insTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.0485984
REMM: 0.049
Frequency Data:
gnomAD_G_AFR: 0.5219%
gnomAD_G_AMR: 0.9148%
gnomAD_G_NFE: 1.6961%
gnomAD_G_SAS: 1.5152%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103824078-G-A [0/1] rs116989294
Variant score: 0.015
Transcripts:
RELN:ENST00000428762.6:c.473+9459C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0162151
REMM: 0.016
Frequency Data:
UK10K: 0.4628%
gnomAD_G_AFR: 0.3109%
gnomAD_G_AMR: 0.2036%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 0.4649%
gnomAD_G_SAS: 0.3944%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103496091-G-A [0/1] rs888316631
Variant score: 0.008
Transcripts:
RELN:ENST00000428762.6:c.9194-193C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00766905
REMM: 0.008
Frequency Data:
gnomAD_G_AMR: 0.0131%
gnomAD_G_NFE: 0.0029%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103910747-T-C [1|1] rs375667749
Variant score: 0.006
Transcripts:
RELN:ENST00000428762.6:c.337+6328A>G:p.(=)
Pathogenicity Data:
Best Score: 0.00555556
REMM: 0.006
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103910734-C-G [1|1] rs201153094
Variant score: 0.005
Transcripts:
RELN:ENST00000428762.6:c.337+6341G>C:p.(=)
Pathogenicity Data:
Best Score: 0.00468056
REMM: 0.005
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103910698-A-G [1/1] rs377741458
Variant score: 0.004
Transcripts:
RELN:ENST00000428762.6:c.337+6377T>C:p.(=)
Pathogenicity Data:
Best Score: 0.00438056
REMM: 0.004
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103873539-T-A [0/1]
Variant score: 0.003
Transcripts:
RELN:ENST00000428762.6:c.338-39867A>T:p.(=)
Pathogenicity Data:
Best Score: 0.00338056
REMM: 0.003
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103564722-C-T [0/1] rs1830710912
Variant score: 0.003
Transcripts:
RELN:ENST00000428762.6:c.5210+556G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00304444
REMM: 0.003
Frequency Data:
gnomAD_G_NFE: 0.0015%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103896371-A-C [0|1] rs968065277
Variant score: 0.001
Transcripts:
RELN:ENST00000428762.6:c.337+20704T>G:p.(=)
Pathogenicity Data:
Best Score: 0.0015
REMM: 0.002
Frequency Data:
gnomAD_G_NFE: 0.0132%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103808416-G-T [0/1]
Variant score: 0.001
Transcripts:
RELN:ENST00000428762.6:c.473+25121C>A:p.(=)
Pathogenicity Data:
Best Score: 6.66667E-4
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103837460-C-G [0/1] rs959629296
Variant score: 0.000
Transcripts:
RELN:ENST00000428762.6:c.338-3788G>C:p.(=)
Pathogenicity Data:
Best Score: 1.42857E-4
REMM: 0.000
Frequency Data:
gnomAD_G_AMR: 0.1504%
gnomAD_G_NFE: 0.0088%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-103554569-CA-C [0/1] rs56319660
Variant score: 0.000
Transcripts:
RELN:ENST00000428762.6:c.5798-739del:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.1542%
gnomAD_G_AMR: 0.0782%
gnomAD_G_EAS: 0.0277%
gnomAD_G_NFE: 0.0777%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-103579599-CA-C [0/1]
Variant score: 0.000
Transcripts:
RELN:ENST00000428762.6:c.4146-3895del:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103783981-C-T [0|1] rs184804267
Variant score: 0.000
Transcripts:
RELN:ENST00000428762.6:c.474-7354G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.4496%
gnomAD_G_AFR: 0.0659%
gnomAD_G_AMR: 0.2013%
gnomAD_G_NFE: 0.4612%
gnomAD_G_SAS: 0.4111%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-103868745-C-T [0/1] rs533102935
Variant score: 0.000
Transcripts:
RELN:ENST00000428762.6:c.338-35073G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.0793%
gnomAD_G_AFR: 0.0144%
gnomAD_G_AMR: 0.2754%
gnomAD_G_NFE: 0.1074%
gnomAD_G_SAS: 0.4141%
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-103904975-C-CTTTTTTT [0/1] rs67024941
Variant score: 0.000
Transcripts:
RELN:ENST00000428762.6:c.337+12099_337+12100insAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-103904975-CT-C [0/1] rs67024941
Variant score: 0.000
Transcripts:
RELN:ENST00000428762.6:c.337+12099del:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data

WT1

Exomiser Score: 0.634 (p=4.8E-2)

Phenotype Score: 0.614

Variant Score: 0.812

Phenotype matches:
Phenotypic similarity 0.614 to 46,XY partial gonadal dysgenesis associated with WT1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Proximity score 0.506 in interactome to SRY and phenotypic similarity 0.614 to 46XX sex reversal 1 associated with SRY.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Known diseases:
OMIM:136680 Frasier syndrome - autosomal dominant
OMIM:156240 Mesothelioma, somatic - somatic
OMIM:194070 Wilms tumor, type 1 - autosomal dominant
OMIM:194080 Denys-Drash syndrome - autosomal dominant
OMIM:256370 Nephrotic syndrome, type 4 - autosomal dominant
OMIM:608978 Meacham syndrome - autosomal dominant
ORPHA:220 Denys-Drash syndrome - autosomal dominant
ORPHA:242 46,XY complete gonadal dysgenesis - autosomal dominant/recessive
ORPHA:251510 46,XY partial gonadal dysgenesis - autosomal dominant/recessive
ORPHA:3097 Meacham syndrome - autosomal dominant
ORPHA:347 Frasier syndrome - autosomal dominant
ORPHA:654 Nephroblastoma (unconfirmed)
ORPHA:654 Nephroblastoma (susceptibility)
ORPHA:656 Genetic steroid-resistant nephrotic syndrome - autosomal dominant
ORPHA:893 WAGR syndrome (CNV)
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.634 (p=4.8E-2)

Phenotype Score: 0.614

Variant Score: 0.812

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.614 to ORPHA:251510 46,XY partial gonadal dysgenesis
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 11-32423587-T-C [0/1] rs568728681
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PP4]
Variant score: 0.888 CONTRIBUTING VARIANT
Transcripts:
WT1:ENST00000452863.10:c.887+4369A>G:p.(=)
Pathogenicity Data:
Best Score: 0.901629
REMM: 0.902
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AFR: 0.0192%
gnomAD_G_NFE: 0.1088%
gnomAD_G_SAS: 0.1036%
CODING_TRANSCRIPT_INTRON_VARIANT INS 11-32411068-T-TACACACACACACACACACACACACAC [0/1] rs10525221
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting, PP4]
Variant score: 0.737 CONTRIBUTING VARIANT
Transcripts:
WT1:ENST00000452863.10:c.1016+5421_1016+5422insGTGTGTGTGTGTGTGTGTGTGTGTGT:p.(=)
Pathogenicity Data:
Best Score: 0.736756
REMM: 0.737
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.464 (p=1.0E-1)

Phenotype Score: 0.614

Variant Score: 0.737

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.614 to ORPHA:251510 46,XY partial gonadal dysgenesis
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 11-32411068-T-TACACACACACACACACACACACACAC [0/1] rs10525221
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting, PP4]
Variant score: 0.737 CONTRIBUTING VARIANT
Transcripts:
WT1:ENST00000452863.10:c.1016+5421_1016+5422insGTGTGTGTGTGTGTGTGTGTGTGTGT:p.(=)
Pathogenicity Data:
Best Score: 0.736756
REMM: 0.737
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 11-32402754-C-T [0|1]
Variant score: 0.392
Transcripts:
WT1:ENST00000452863.10:c.1017-2710G>A:p.(=)
Pathogenicity Data:
Best Score: 0.392435
REMM: 0.392
Frequency Data:
No frequency data

INSR

Exomiser Score: 0.630 (p=4.9E-2)

Phenotype Score: 0.620

Variant Score: 0.803

Phenotype matches:
Phenotypic similarity 0.620 to Leprechaunism associated with INSR.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0004405, Prominent nipples
HP:0006625, Multifocal breast carcinoma - HP:0004405, Prominent nipples
Phenotypic similarity 0.273 to zebrafish mutant involving INSR.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0103759, scale fin decreased size, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0103759, scale fin decreased size, abnormal
Proximity score 0.503 in interactome to FGF17 and phenotypic similarity 0.620 to Kallmann syndrome associated with FGF17.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003187, Breast hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0003187, Breast hypoplasia
Known diseases:
OMIM:246200 Donohue syndrome - autosomal recessive
OMIM:262190 Rabson-Mendenhall syndrome - autosomal recessive
OMIM:609968 Hyperinsulinemic hypoglycemia, familial, 5 - autosomal dominant
ORPHA:2297 Insulin-resistance syndrome type A - autosomal dominant/recessive
ORPHA:263458 Hyperinsulinism due to INSR deficiency - autosomal dominant
ORPHA:508 Leprechaunism - autosomal recessive
ORPHA:769 Rabson-Mendenhall syndrome - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.630 (p=4.9E-2)

Phenotype Score: 0.620

Variant Score: 0.803

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.620 to ORPHA:508 Leprechaunism
Phenotypic similarity 0.620 to OMIM:246200 Donohue syndrome
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 19-7206951-G-A [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting, PP4]
Variant score: 0.906 CONTRIBUTING VARIANT
Transcripts:
INSR:ENST00000302850.10:c.653-22314C>T:p.(=)
Pathogenicity Data:
Best Score: 0.90557
REMM: 0.906
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 19-7207901-A-AAAGGAAGG [0/1] rs35679001
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting, PP4]
Variant score: 0.700 CONTRIBUTING VARIANT
Transcripts:
INSR:ENST00000302850.10:c.653-23265_653-23264insCCTTCCTT:p.(=)
Pathogenicity Data:
Best Score: 0.699517
REMM: 0.700
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.565 (p=7.0E-2)

Phenotype Score: 0.503

Variant Score: 0.906

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 19-7206951-G-A [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.906 CONTRIBUTING VARIANT
Transcripts:
INSR:ENST00000302850.10:c.653-22314C>T:p.(=)
Pathogenicity Data:
Best Score: 0.90557
REMM: 0.906
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 19-7225441-G-T [0/1] rs184558049
Variant score: 0.670
Transcripts:
INSR:ENST00000302850.10:c.653-40804C>A:p.(=)
Pathogenicity Data:
Best Score: 0.674651
REMM: 0.675
Frequency Data:
UK10K: 0.0397%
gnomAD_G_AFR: 0.0100%
gnomAD_G_AMR: 0.0274%
gnomAD_G_NFE: 0.0530%
gnomAD_G_SAS: 0.0483%
REGULATORY_REGION_VARIANT SNV 19-7674571-G-A [0/1]
Variant score: 0.658
Transcripts:
Pathogenicity Data:
Best Score: 0.658115
REMM: 0.658
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 19-7188870-CA-C [0/1] rs10549803
Variant score: 0.629
Transcripts:
INSR:ENST00000302850.10:c.653-4234del:p.(=)
Pathogenicity Data:
Best Score: 0.62866
REMM: 0.629
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 19-7181182-G-A [0/1] rs865964237
Variant score: 0.590
Transcripts:
INSR:ENST00000302850.10:c.974+3134C>T:p.(=)
Pathogenicity Data:
Best Score: 0.593127
REMM: 0.593
Frequency Data:
gnomAD_G_AFR: 0.0072%
gnomAD_G_AMR: 0.0261%
gnomAD_G_NFE: 0.0412%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 19-7192261-AGAAAAGAAAAGAAAAG-A [0|1]
Variant score: 0.574
Transcripts:
INSR:ENST00000302850.10:c.653-7640_653-7625del:p.(=)
Pathogenicity Data:
Best Score: 0.574192
REMM: 0.574
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 19-7192256-AG-A [0|1]
Variant score: 0.520
Transcripts:
INSR:ENST00000302850.10:c.653-7620del:p.(=)
Pathogenicity Data:
Best Score: 0.520137
REMM: 0.520
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 19-7213356-A-AAC [0/1] rs1555753426
Variant score: 0.500
Transcripts:
INSR:ENST00000302850.10:c.653-28720_653-28719insGT:p.(=)
Pathogenicity Data:
Best Score: 0.61876
REMM: 0.619
Frequency Data:
gnomAD_G_AFR: 0.8826%
gnomAD_G_AMR: 0.4120%
gnomAD_G_EAS: 0.1182%
gnomAD_G_NFE: 0.3734%
gnomAD_G_SAS: 0.7331%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 19-7238962-CAAAA-C [0/1]
Variant score: 0.456
Transcripts:
INSR:ENST00000302850.10:c.652+28379_652+28382del:p.(=)
Pathogenicity Data:
Best Score: 0.455689
REMM: 0.456
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 19-7238962-C-CAAA [0/1]
Variant score: 0.432
Transcripts:
INSR:ENST00000302850.10:c.652+28382_652+28383insTTT:p.(=)
Pathogenicity Data:
Best Score: 0.431873
REMM: 0.432
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 19-7229760-CT-C [0/1] rs71177180
Variant score: 0.404
Transcripts:
INSR:ENST00000302850.10:c.652+37584del:p.(=)
Pathogenicity Data:
Best Score: 0.403928
REMM: 0.404
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 19-7243234-GT-G [1/1] rs1161289283
Variant score: 0.385
Transcripts:
INSR:ENST00000302850.10:c.652+24110del:p.(=)
Pathogenicity Data:
Best Score: 0.384757
REMM: 0.385
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 19-7238617-C-CAAA [0/1]
Variant score: 0.347
Transcripts:
INSR:ENST00000302850.10:c.652+28727_652+28728insTTT:p.(=)
Pathogenicity Data:
Best Score: 0.347206
REMM: 0.347
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 19-7185841-C-CAAAAAAAAAA [1/1]
Variant score: 0.329
Transcripts:
INSR:ENST00000302850.10:c.653-1205_653-1204insTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.328858
REMM: 0.329
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 19-7197516-G-GTGTGTGTGTGTGTGTGTGT [1|0] rs1568480264
Variant score: 0.301
Transcripts:
INSR:ENST00000302850.10:c.653-12880_653-12879insACACACACACACACACACA:p.(=)
Pathogenicity Data:
Best Score: 0.447916
REMM: 0.448
Frequency Data:
gnomAD_G_AFR: 0.4569%
gnomAD_G_AMR: 1.2320%
gnomAD_G_EAS: 0.1988%
gnomAD_G_NFE: 0.9542%
gnomAD_G_SAS: 0.7781%
CODING_TRANSCRIPT_INTRON_VARIANT INS 19-7137798-C-CAA [1/1]
Variant score: 0.292
Transcripts:
INSR:ENST00000302850.10:c.2682+3878_2682+3879insTT:p.(=)
Pathogenicity Data:
Best Score: 0.291638
REMM: 0.292
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 19-7142389-CA-C [0/1] rs34453877
Variant score: 0.247
Transcripts:
INSR:ENST00000302850.10:c.2542+426del:p.(=)
Pathogenicity Data:
Best Score: 0.246877
REMM: 0.247
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 19-7194508-CT-C [0/1] rs35025189
Variant score: 0.214
Transcripts:
INSR:ENST00000302850.10:c.653-9872del:p.(=)
Pathogenicity Data:
Best Score: 0.214255
REMM: 0.214
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 19-7156782-CT-C [1/1] rs746400499
Variant score: 0.186
Transcripts:
INSR:ENST00000302850.10:c.2030-3856del:p.(=)
Pathogenicity Data:
Best Score: 0.185744
REMM: 0.186
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 19-7269038-C-CCACACACACACA [0/1] rs141333611
Variant score: 0.126
Transcripts:
INSR:ENST00000302850.10:c.101-1143_101-1142insTGTGTGTGTGTG:p.(=)
Pathogenicity Data:
Best Score: 0.463199
REMM: 0.463
Frequency Data:
gnomAD_G_AFR: 0.1405%
gnomAD_G_AMR: 0.4663%
gnomAD_G_EAS: 1.6400%
gnomAD_G_NFE: 0.5404%
gnomAD_G_SAS: 1.8526%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 19-7118914-CAA-C [0/1]
Variant score: 0.052
Transcripts:
INSR:ENST00000302850.10:c.3794+533_3794+534del:p.(=)
Pathogenicity Data:
Best Score: 0.0524571
REMM: 0.052
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 19-7118914-CA-C [0/1]
Variant score: 0.005
Transcripts:
INSR:ENST00000302850.10:c.3794+534del:p.(=)
Pathogenicity Data:
Best Score: 0.00486111
REMM: 0.005
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 19-7256931-CT-C [0/1] rs772500676
Variant score: 0.002
Transcripts:
INSR:ENST00000302850.10:c.652+10413del:p.(=)
Pathogenicity Data:
Best Score: 0.00240833
REMM: 0.002
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 19-7226728-C-CAAAAAAA [0/1]
Variant score: 0.002
Transcripts:
INSR:ENST00000302850.10:c.652+40616_652+40617insTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.001625
REMM: 0.002
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 19-7199560-C-CTTTT [0/1] rs3084138
Variant score: 0.001
Transcripts:
INSR:ENST00000302850.10:c.653-14924_653-14923insAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.00125
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 19-7219487-A-G [1/1] rs12985490
Variant score: 0.000
Transcripts:
INSR:ENST00000302850.10:c.653-34850T>C:p.(=)
Pathogenicity Data:
Best Score: 3.88889E-4
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 19-7233668-CT-C [1/1] rs35763064
Variant score: 0.000
Transcripts:
INSR:ENST00000302850.10:c.652+33676del:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data

EYA1

Exomiser Score: 0.616 (p=5.4E-2)

Phenotype Score: 0.501

Variant Score: 0.931

Phenotype matches:
Phenotypic similarity 0.414 to ?Otofaciocervical syndrome associated with EYA1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0200021, Down-sloping shoulders
HP:0006625, Multifocal breast carcinoma - HP:0200021, Down-sloping shoulders
Phenotypic similarity 0.342 to mouse mutant involving EYA1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000154, rib fusion
HP:0006625, Multifocal breast carcinoma - MP:0000154, rib fusion
Phenotypic similarity 0.256 to zebrafish mutant involving EYA1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0001052, mandibular arch skeleton morphology, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0001052, mandibular arch skeleton morphology, abnormal
Proximity score 0.501 in interactome to ERBB2 and phenotypic similarity 0.998 to Ovarian cancer, somatic associated with ERBB2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Known diseases:
OMIM:113650 Branchiootorenal syndrome 1, with or without cataracts - autosomal dominant
OMIM:166780 ?Otofaciocervical syndrome (unconfirmed)
OMIM:602588 Branchiootic syndrome 1 - autosomal dominant
ORPHA:107 BOR syndrome - autosomal dominant
ORPHA:2792 Otofaciocervical syndrome - autosomal dominant
ORPHA:52429 Branchiootic syndrome - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.616 (p=5.4E-2)

Phenotype Score: 0.501

Variant Score: 0.931

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.414 to OMIM:166780 ?Otofaciocervical syndrome
Phenotypic similarity 0.411 to ORPHA:2792 Otofaciocervical syndrome
Variants contributing to score:
THREE_PRIME_UTR_EXON_VARIANT SNV 8-71198056-G-T [0/1] rs867048052
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.931 CONTRIBUTING VARIANT
Transcripts:
EYA1:ENST00000340726.8:c.*1284C>A:p.(=)
Pathogenicity Data:
Best Score: 0.934732
REMM: 0.935
Frequency Data:
gnomAD_G_AMR: 0.0262%
gnomAD_G_NFE: 0.0162%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.025 (p=3.8E-1)

Phenotype Score: 0.251

Variant Score: 0.762

No phenotype matches to diseases with this MOI.
Variants contributing to score:
THREE_PRIME_UTR_EXON_VARIANT SNV 8-71198056-G-T [0/1] rs867048052
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.931 CONTRIBUTING VARIANT
Transcripts:
EYA1:ENST00000340726.8:c.*1284C>A:p.(=)
Pathogenicity Data:
Best Score: 0.934732
REMM: 0.935
Frequency Data:
gnomAD_G_AMR: 0.0262%
gnomAD_G_NFE: 0.0162%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-71286797-GT-G [0/1] rs141777395
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.593 CONTRIBUTING VARIANT
Transcripts:
EYA1:ENST00000340726.8:c.826+12249del:p.(=)
Pathogenicity Data:
Best Score: 0.593446
REMM: 0.593
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-71286797-GTT-G [0/1] rs141777395
Variant score: 0.593
Transcripts:
EYA1:ENST00000340726.8:c.826+12248_826+12249del:p.(=)
Pathogenicity Data:
Best Score: 0.593446
REMM: 0.593
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-71277115-ATTTTTT-A [0/1]
Variant score: 0.505
Transcripts:
EYA1:ENST00000340726.8:c.827-5224_827-5219del:p.(=)
Pathogenicity Data:
Best Score: 0.505493
REMM: 0.505
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-71277115-AT-A [0/1]
Variant score: 0.238
Transcripts:
EYA1:ENST00000340726.8:c.827-5219del:p.(=)
Pathogenicity Data:
Best Score: 0.238122
REMM: 0.238
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-71331489-T-TTATATATA [0/1] rs71264550
Variant score: 0.227
Transcripts:
EYA1:ENST00000340726.8:c.202+2607_202+2608insTATATATA:p.(=)
Pathogenicity Data:
Best Score: 0.367178
REMM: 0.367
Frequency Data:
gnomAD_G_AFR: 0.3395%
gnomAD_G_AMR: 0.9940%
gnomAD_G_EAS: 0.4741%
gnomAD_G_NFE: 0.7595%
gnomAD_G_SAS: 1.3427%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-71245153-C-T [0/1] rs62507633
Variant score: 0.034
Transcripts:
EYA1:ENST00000340726.8:c.1051-461G>A:p.(=)
Pathogenicity Data:
Best Score: 0.226455
REMM: 0.226
Frequency Data:
UK10K: 1.9836%
gnomAD_G_AFR: 0.3248%
gnomAD_G_AMR: 1.2418%
gnomAD_G_EAS: 0.1160%
gnomAD_G_NFE: 1.8672%
gnomAD_G_SAS: 0.1449%

ITPR1

Exomiser Score: 0.611 (p=5.5E-2)

Phenotype Score: 0.504

Variant Score: 0.926

Phenotype matches:
Proximity score 0.504 in interactome to RASGRP1 and phenotypic similarity 0.876 to Autoimmune lymphoproliferative syndrome associated with RASGRP1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010619, Fibroadenoma of the breast
HP:0006625, Multifocal breast carcinoma - HP:0010619, Fibroadenoma of the breast
Proximity score 0.504 in interactome to RASGRP1 and phenotypic similarity 0.207 to mouse mutant of RASGRP1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002145, abnormal T cell differentiation
HP:0006625, Multifocal breast carcinoma - MP:0002145, abnormal T cell differentiation
Known diseases:
OMIM:117360 Spinocerebellar ataxia 29, congenital nonprogressive - autosomal dominant
OMIM:206700 Gillespie syndrome - autosomal dominant/recessive
OMIM:606658 Spinocerebellar ataxia 15 - autosomal dominant
ORPHA:1065 Aniridia-cerebellar ataxia-intellectual disability syndrome - autosomal dominant/recessive
ORPHA:208513 Spinocerebellar ataxia type 29 - autosomal dominant
ORPHA:98769 Spinocerebellar ataxia type 15/16 - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.611 (p=5.5E-2)

Phenotype Score: 0.504

Variant Score: 0.926

No phenotype matches to diseases with this MOI.
Variants contributing to score:
THREE_PRIME_UTR_EXON_VARIANT INS 3-4847395-C-CAA [1/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.926 CONTRIBUTING VARIANT
Transcripts:
ITPR1:ENST00000649015.2:c.*1183_*1184dup:p.(=)
Pathogenicity Data:
Best Score: 0.925518
REMM: 0.926
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.192 (p=2.0E-1)

Phenotype Score: 0.504

Variant Score: 0.720

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 3-4711210-CAAAAA-C [0/1] rs1169754547
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.720 CONTRIBUTING VARIANT
Transcripts:
ITPR1:ENST00000649015.2:c.4992-546_4992-542del:p.(=)
Pathogenicity Data:
Best Score: 0.722664
REMM: 0.723
Frequency Data:
gnomAD_G_AFR: 0.0276%
gnomAD_G_NFE: 0.0177%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 3-4807110-GCTTACAAAGAGAGGGGGGCTTACAAAGAGAGGGGGGA-G [1/1] rs534474592
Variant score: 0.808
Transcripts:
ITPR1:ENST00000649015.2:c.7272+844_7272+880del:p.(=)
Pathogenicity Data:
Best Score: 0.808235
REMM: 0.808
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-4773714-A-T [0/1] rs77109297
Variant score: 0.643
Transcripts:
ITPR1:ENST00000649015.2:c.5980-1528A>T:p.(=)
Pathogenicity Data:
Best Score: 0.853785
REMM: 0.854
Frequency Data:
UK10K: 0.9654%
gnomAD_G_AFR: 0.2117%
gnomAD_G_AMR: 0.3268%
gnomAD_G_NFE: 1.0380%
gnomAD_G_SAS: 0.2280%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 3-4744942-TTCCTTCCC-T [0/1] rs147105178
Variant score: 0.641
Transcripts:
ITPR1:ENST00000649015.2:c.5544+9589_5544+9596del:p.(=)
Pathogenicity Data:
Best Score: 0.641311
REMM: 0.641
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-4535028-G-A [0/1] rs78696619
Variant score: 0.636
Transcripts:
ITPR1:ENST00000649015.2:c.163+13934G>A:p.(=)
Pathogenicity Data:
Best Score: 0.858267
REMM: 0.858
Frequency Data:
UK10K: 0.6083%
gnomAD_G_AFR: 0.1617%
gnomAD_G_AMR: 1.0684%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.7758%
gnomAD_G_SAS: 0.6434%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-4523405-A-G [0/1]
Variant score: 0.563
Transcripts:
ITPR1:ENST00000649015.2:c.163+2311A>G:p.(=)
Pathogenicity Data:
Best Score: 0.563462
REMM: 0.563
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-4801635-G-A [0/1]
Variant score: 0.527
Transcripts:
ITPR1:ENST00000649015.2:c.7107+1035G>A:p.(=)
Pathogenicity Data:
Best Score: 0.526976
REMM: 0.527
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 3-4499996-C-T [0/1] rs114238636
Variant score: 0.519
Transcripts:
ITPR1:ENST00000649015.2:c.-17+5490C>T:p.(=)
Pathogenicity Data:
Best Score: 0.665906
REMM: 0.666
Frequency Data:
UK10K: 0.8199%
gnomAD_G_AFR: 0.1974%
gnomAD_G_AMR: 0.9678%
gnomAD_G_NFE: 0.9100%
gnomAD_G_SAS: 0.1451%
CODING_TRANSCRIPT_INTRON_VARIANT INS 3-4611025-T-TCCTC [0/1]
Variant score: 0.500
Transcripts:
ITPR1:ENST00000649015.2:c.164-16738_164-16737insCCTC:p.(=)
Pathogenicity Data:
Best Score: 0.499607
REMM: 0.500
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 3-4611025-TCCTCCCTC-T [0/1]
Variant score: 0.500
Transcripts:
ITPR1:ENST00000649015.2:c.164-16737_164-16730del:p.(=)
Pathogenicity Data:
Best Score: 0.499607
REMM: 0.500
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-4557354-G-A [0/1] rs538684428
Variant score: 0.489
Transcripts:
ITPR1:ENST00000649015.2:c.163+36260G>A:p.(=)
Pathogenicity Data:
Best Score: 0.63965
REMM: 0.640
Frequency Data:
UK10K: 0.7802%
gnomAD_G_AFR: 0.1781%
gnomAD_G_AMR: 1.0064%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.9177%
gnomAD_G_SAS: 0.1246%
INTERGENIC_VARIANT INS 3-4480534-C-CAATAATAATAAT [0/1] rs61696982
Variant score: 0.458
Transcripts:
ITPR1:ENST00000649015.2::
Pathogenicity Data:
Best Score: 0.458368
REMM: 0.458
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 3-4616355-TTATA-T [0/1] rs559864676
Variant score: 0.382
Transcripts:
ITPR1:ENST00000649015.2:c.164-11407_164-11404del:p.(=)
Pathogenicity Data:
Best Score: 0.728404
REMM: 0.728
Frequency Data:
UK10K: 1.5075%
gnomAD_G_AFR: 0.2357%
gnomAD_G_AMR: 0.7518%
gnomAD_G_NFE: 1.4345%
gnomAD_G_SAS: 1.3900%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-4803930-G-A [0/1] rs145899651
Variant score: 0.235
Transcripts:
ITPR1:ENST00000649015.2:c.7108-2173G>A:p.(=)
Pathogenicity Data:
Best Score: 0.295799
REMM: 0.296
Frequency Data:
UK10K: 0.8728%
gnomAD_G_AFR: 0.2021%
gnomAD_G_AMR: 0.3855%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.9221%
gnomAD_G_SAS: 0.2281%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 3-4787337-CA-C [1/1]
Variant score: 0.220
Transcripts:
ITPR1:ENST00000649015.2:c.6616-609del:p.(=)
Pathogenicity Data:
Best Score: 0.219624
REMM: 0.220
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 3-4609089-T-TATATATAC [0/1] rs1171860541
Variant score: 0.206
Transcripts:
ITPR1:ENST00000649015.2:c.164-18674_164-18673insATATATAC:p.(=)
Pathogenicity Data:
Best Score: 0.207997
REMM: 0.208
Frequency Data:
gnomAD_G_AFR: 0.0113%
gnomAD_G_AMR: 0.0824%
gnomAD_G_NFE: 0.0760%
INTERGENIC_VARIANT SNV 3-4483362-T-C [0/1] rs780353768
Variant score: 0.152
Transcripts:
ITPR1:ENST00000649015.2::
Pathogenicity Data:
Best Score: 0.152346
REMM: 0.152
Frequency Data:
gnomAD_G_NFE: 0.0088%
INTERGENIC_VARIANT DEL 3-4482796-CT-C [0/1] rs35930607
Variant score: 0.137
Transcripts:
ITPR1:ENST00000649015.2::
Pathogenicity Data:
Best Score: 0.136542
REMM: 0.137
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-4589639-T-G [0/1] rs140725255
Variant score: 0.125
Transcripts:
ITPR1:ENST00000649015.2:c.164-38124T>G:p.(=)
Pathogenicity Data:
Best Score: 0.536178
REMM: 0.536
Frequency Data:
UK10K: 0.8728%
gnomAD_G_AFR: 0.1302%
gnomAD_G_AMR: 0.6887%
gnomAD_G_NFE: 0.9769%
gnomAD_G_SAS: 1.8966%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-4824614-G-A [0/1] rs989282603
Variant score: 0.005
Transcripts:
ITPR1:ENST00000649015.2:c.8028+6372G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00470357
REMM: 0.005
Frequency Data:
gnomAD_G_AFR: 0.0217%
gnomAD_G_AMR: 0.0065%
gnomAD_G_NFE: 0.0015%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-4599950-T-C [0/1] rs2091142706
Variant score: 0.003
Transcripts:
ITPR1:ENST00000649015.2:c.164-27813T>C:p.(=)
Pathogenicity Data:
Best Score: 0.00282222
REMM: 0.003
Frequency Data:
gnomAD_G_NFE: 0.0015%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-4583187-C-T [0/1] rs141571039
Variant score: 0.002
Transcripts:
ITPR1:ENST00000649015.2:c.164-44576C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00287222
REMM: 0.003
Frequency Data:
UK10K: 0.3174%
gnomAD_G_AFR: 0.0530%
gnomAD_G_AMR: 0.1570%
gnomAD_G_NFE: 0.2985%
gnomAD_G_SAS: 0.7258%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-4622975-C-T [0/1] rs143058475
Variant score: 0.001
Transcripts:
ITPR1:ENST00000649015.2:c.164-4788C>T:p.(=)
Pathogenicity Data:
Best Score: 8.38095E-4
REMM: 0.001
Frequency Data:
UK10K: 1.1769%
gnomAD_G_AFR: 0.2381%
gnomAD_G_AMR: 1.0003%
gnomAD_G_NFE: 1.2199%
gnomAD_G_SAS: 0.7667%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-4655854-G-A [0/1] rs148580378
Variant score: 0.001
Transcripts:
ITPR1:ENST00000649015.2:c.996+1968G>A:p.(=)
Pathogenicity Data:
Best Score: 9.16667E-4
REMM: 0.001
Frequency Data:
UK10K: 0.0264%
gnomAD_G_AFR: 1.3816%
gnomAD_G_AMR: 0.1765%
gnomAD_G_NFE: 0.0970%
gnomAD_G_SAS: 0.1867%
INTERGENIC_VARIANT DEL 3-4483663-CT-C [0/1] rs536035821
Variant score: 0.000
Transcripts:
ITPR1:ENST00000649015.2::
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-4557038-C-T [0/1] rs910131754
Variant score: 0.000
Transcripts:
ITPR1:ENST00000649015.2:c.163+35944C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0131%
gnomAD_G_NFE: 0.0191%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-4557280-A-G [0/1] rs148813434
Variant score: 0.000
Transcripts:
ITPR1:ENST00000649015.2:c.163+36186A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.7934%
gnomAD_G_AFR: 0.1804%
gnomAD_G_AMR: 1.0463%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.9306%
gnomAD_G_SAS: 0.7054%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-4580263-G-C [0/1] rs774554510
Variant score: 0.000
Transcripts:
ITPR1:ENST00000649015.2:c.164-47500G>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_NFE: 0.0103%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-4605633-C-T [0/1] rs778354961
Variant score: 0.000
Transcripts:
ITPR1:ENST00000649015.2:c.164-22130C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.0397%
gnomAD_G_AFR: 0.0024%
gnomAD_G_NFE: 0.0294%
CODING_TRANSCRIPT_INTRON_VARIANT INS 3-4829954-G-GT [0/1]
Variant score: 0.000
Transcripts:
ITPR1:ENST00000649015.2:c.8029-6820_8029-6819insT:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data

ZEB2

Exomiser Score: 0.610 (p=5.6E-2)

Phenotype Score: 0.577

Variant Score: 0.843

Phenotype matches:
Phenotypic similarity 0.577 to Mowat-Wilson syndrome associated with ZEB2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0002558, Supernumerary nipple
HP:0006625, Multifocal breast carcinoma - HP:0002558, Supernumerary nipple
Phenotypic similarity 0.242 to zebrafish mutant involving ZEB2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0000235, mandibular arch skeleton hypoplastic, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0000235, mandibular arch skeleton hypoplastic, abnormal
Proximity score 0.504 in interactome to TWIST1 and phenotypic similarity 0.998 to Saethre-Chotzen syndrome with or without eyelid anomalies associated with TWIST1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.504 in interactome to TWIST1 and phenotypic similarity 0.356 to mouse mutant of TWIST1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000137, abnormal vertebrae morphology
HP:0006625, Multifocal breast carcinoma - MP:0000137, abnormal vertebrae morphology
Proximity score 0.504 in interactome to TWIST1 and phenotypic similarity 0.257 to fish mutant of TWIST1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0007632, notochord absent, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0007632, notochord absent, abnormal
Known diseases:
OMIM:235730 Mowat-Wilson syndrome - autosomal dominant
ORPHA:261537 Mowat-Wilson syndrome due to monosomy 2q22 (CNV)
ORPHA:261552 Mowat-Wilson syndrome due to a ZEB2 point mutation - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.610 (p=5.6E-2)

Phenotype Score: 0.577

Variant Score: 0.843

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.577 to OMIM:235730 Mowat-Wilson syndrome
Phenotypic similarity 0.463 to ORPHA:261537 Mowat-Wilson syndrome due to monosomy 2q22
Phenotypic similarity 0.463 to ORPHA:261552 Mowat-Wilson syndrome due to a ZEB2 point mutation
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 2-144414257-ATTC-A [0/1] rs1380616286
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.843 CONTRIBUTING VARIANT
Transcripts:
ZEB2:ENST00000627532.3:c.404-9236_404-9234del:p.(=)
Pathogenicity Data:
Best Score: 0.842781
REMM: 0.843
Frequency Data:
gnomAD_G_NFE: 0.0015%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.042 (p=3.4E-1)

Phenotype Score: 0.252

Variant Score: 0.820

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 2-144414257-ATTC-A [0/1] rs1380616286
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.843 CONTRIBUTING VARIANT
Transcripts:
ZEB2:ENST00000627532.3:c.404-9236_404-9234del:p.(=)
Pathogenicity Data:
Best Score: 0.842781
REMM: 0.843
Frequency Data:
gnomAD_G_NFE: 0.0015%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-144450926-C-A [0/1] rs189392529
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.798 CONTRIBUTING VARIANT
Transcripts:
ZEB2:ENST00000627532.3:c.74-20900G>T:p.(=)
Pathogenicity Data:
Best Score: 0.815095
REMM: 0.815
Frequency Data:
gnomAD_G_AMR: 0.0719%
gnomAD_G_NFE: 0.0441%
gnomAD_G_SAS: 0.1450%
Other passed variants:
REGULATORY_REGION_VARIANT INS 2-144703846-C-CAA [0/1]
Variant score: 0.746
Transcripts:
ZEB2:ENST00000627532.3::
Pathogenicity Data:
Best Score: 0.745971
REMM: 0.746
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-144429083-C-T [0/1] rs144552188
Variant score: 0.719
Transcripts:
ZEB2:ENST00000627532.3:c.331+686G>A:p.(=)
Pathogenicity Data:
Best Score: 0.725536
REMM: 0.726
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0654%
gnomAD_G_NFE: 0.0103%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-144460969-A-G [0/1] rs116044364
Variant score: 0.690
Transcripts:
ZEB2:ENST00000627532.3:c.74-30943T>C:p.(=)
Pathogenicity Data:
Best Score: 0.977721
REMM: 0.978
Frequency Data:
UK10K: 0.8463%
gnomAD_G_AFR: 0.1587%
gnomAD_G_AMR: 0.4777%
gnomAD_G_NFE: 1.1542%
gnomAD_G_SAS: 0.6829%
REGULATORY_REGION_VARIANT SNV 2-144683641-C-G [0/1]
Variant score: 0.673
Transcripts:
ZEB2:ENST00000627532.3::
Pathogenicity Data:
Best Score: 0.672731
REMM: 0.673
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 2-144498058-A-AATATATT [0/1]
Variant score: 0.010
Transcripts:
ZEB2:ENST00000627532.3:c.73+19219_73+19220insAATATAT:p.(=)
Pathogenicity Data:
Best Score: 0.00960556
REMM: 0.010
Frequency Data:
No frequency data
DOWNSTREAM_GENE_VARIANT DEL 2-144383543-GT-G [0/1] rs151101138
Variant score: 0.004
Transcripts:
ZEB2:ENST00000627532.3::
Pathogenicity Data:
Best Score: 0.00955079
REMM: 0.010
Frequency Data:
gnomAD_G_AFR: 0.9689%
gnomAD_G_AMR: 0.6405%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 1.2279%
gnomAD_G_SAS: 1.6534%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 2-144497832-TATATATATATATGTCATTCTCAACATATATATATATATGTCATTCTCAAC-T [1/1] nsv1114142
Variant score: 0.000
Transcripts:
ZEB2:ENST00000627532.3:c.73+19396_73+19445del:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data

ATN1

Exomiser Score: 0.524 (p=8.3E-2)

Phenotype Score: 0.643

Variant Score: 0.730

Phenotype matches:
Phenotypic similarity 0.643 to Congenital hypotonia, epilepsy, developmental delay, and digital anomalies associated with ATN1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Proximity score 0.502 in interactome to RERE and phenotypic similarity 0.643 to Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart associated with RERE.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Proximity score 0.502 in interactome to RERE and phenotypic similarity 0.260 to fish mutant of RERE.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0001988, neurocranium decreased size, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0001988, neurocranium decreased size, abnormal
Known diseases:
OMIM:125370 Dentatorubral-pallidoluysian atrophy - autosomal dominant
OMIM:618494 Congenital hypotonia, epilepsy, developmental delay, and digital anomalies - autosomal dominant
ORPHA:101 Dentatorubral pallidoluysian atrophy - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.524 (p=8.3E-2)

Phenotype Score: 0.643

Variant Score: 0.730

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.643 to OMIM:618494 Congenital hypotonia, epilepsy, developmental delay, and digital anomalies
Variants contributing to score:
FIVE_PRIME_UTR_INTRON_VARIANT DEL 12-6932034-CAA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting, PP4]
Variant score: 0.730 CONTRIBUTING VARIANT
Transcripts:
ATN1:ENST00000396684.3:c.-162-1805_-162-1804del:p.(=)
Pathogenicity Data:
Best Score: 0.729988
REMM: 0.730
Frequency Data:
No frequency data

FANCM

Exomiser Score: 0.507 (p=8.8E-2)

Phenotype Score: 0.514

Variant Score: 0.868

Phenotype matches:
Proximity score 0.514 in interactome to NTHL1 and phenotypic similarity 0.998 to Familial adenomatous polyposis 3 associated with NTHL1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Known diseases:
OMIM:618086 Spermatogenic failure 28 - autosomal recessive
OMIM:618096 ?Premature ovarian failure 15 (unconfirmed)
ORPHA:399805 Male infertility with azoospermia or oligozoospermia due to single gene mutation - autosomal recessive
ORPHA:84 Fanconi anemia - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.507 (p=8.8E-2)

Phenotype Score: 0.514

Variant Score: 0.868

No phenotype matches to diseases with this MOI.
Variants contributing to score:
STOP_GAINED SNV 14-45176675-T-A [0/1]
Exomiser ACMG: LIKELY_PATHOGENIC [PVS1, PM2_Supporting]
Variant score: 1.000 CONTRIBUTING VARIANT
Transcripts:
FANCM:ENST00000267430.10:c.3921T>A:p.(Tyr1307*)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 14-45152212-TAGAG-T [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.737 CONTRIBUTING VARIANT
Transcripts:
FANCM:ENST00000267430.10:c.1050+685_1050+688del:p.(=)
Pathogenicity Data:
Best Score: 0.736866
REMM: 0.737
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.192 (p=2.0E-1)

Phenotype Score: 0.257

Variant Score: 1.000

No phenotype matches to diseases with this MOI.
Variants contributing to score:
STOP_GAINED SNV 14-45176675-T-A [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 1.000 CONTRIBUTING VARIANT
Transcripts:
FANCM:ENST00000267430.10:c.3921T>A:p.(Tyr1307*)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 14-45146832-CA-C [0/1]
Variant score: 0.161
Transcripts:
FANCM:ENST00000267430.10:c.760-2004del:p.(=)
Pathogenicity Data:
Best Score: 0.160904
REMM: 0.161
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 14-45148200-A-ACACACACACAC [0/1] rs1566731408
Variant score: 0.152
Transcripts:
FANCM:ENST00000267430.10:c.760-637_760-636insCACACACACAC:p.(=)
Pathogenicity Data:
Best Score: 0.223978
REMM: 0.224
Frequency Data:
gnomAD_G_AFR: 0.0859%
gnomAD_G_AMR: 0.6191%
gnomAD_G_EAS: 0.2466%
gnomAD_G_NFE: 0.4159%
gnomAD_G_SAS: 1.2195%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-45160206-G-A [0/1] rs954720722
Variant score: 0.000
Transcripts:
FANCM:ENST00000267430.10:c.1581+926G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AMR: 0.0132%
gnomAD_G_NFE: 0.0133%
gnomAD_G_SAS: 0.1043%

VWF

Exomiser Score: 0.498 (p=9.1E-2)

Phenotype Score: 0.502

Variant Score: 0.878

Phenotype matches:
Proximity score 0.502 in interactome to ITGA3 and phenotypic similarity 0.603 to Epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome associated with ITGA3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Known diseases:
OMIM:193400 von Willebrand disease, type 1 - autosomal dominant
OMIM:277480 von Willebrand disease, type 3 - autosomal recessive
OMIM:613554 von Willebrand disease, types 2A, 2B, 2M, and 2N - autosomal dominant/recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.498 (p=9.1E-2)

Phenotype Score: 0.502

Variant Score: 0.878

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-6056293-T-TCCAGCCACCCAAGGGACCAGAGAGTGGGAGC [0/1] rs145312072
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.878 CONTRIBUTING VARIANT
Transcripts:
VWF:ENST00000261405.10:c.1945+563_1945+564insGCTCCCACTCTCTGGTCCCTTGGGTGGCTGG:p.(=)
Pathogenicity Data:
Best Score: 0.878489
REMM: 0.878
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.451 (p=1.0E-1)

Phenotype Score: 0.502

Variant Score: 0.858

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-6056293-T-TCCAGCCACCCAAGGGACCAGAGAGTGGGAGC [0/1] rs145312072
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.878 CONTRIBUTING VARIANT
Transcripts:
VWF:ENST00000261405.10:c.1945+563_1945+564insGCTCCCACTCTCTGGTCCCTTGGGTGGCTGG:p.(=)
Pathogenicity Data:
Best Score: 0.878489
REMM: 0.878
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-6058531-A-T [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.838 CONTRIBUTING VARIANT
Transcripts:
VWF:ENST00000261405.10:c.1534-487T>A:p.(=)
Pathogenicity Data:
Best Score: 0.837626
REMM: 0.838
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-6019779-G-A [0/1] rs370897964
Variant score: 0.676
Transcripts:
VWF:ENST00000261405.10:c.3675-36C>T:p.(=)
Pathogenicity Data:
Best Score: 0.685096
REMM: 0.685
Frequency Data:
gnomAD_E_AFR: 0.0121%
gnomAD_E_NFE: 0.0079%
gnomAD_E_SAS: 0.0919%
gnomAD_G_AFR: 0.0289%
gnomAD_G_AMR: 0.0065%
gnomAD_G_NFE: 0.0103%
gnomAD_G_SAS: 0.0830%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-6118376-CT-C [0/1] rs71064189
Variant score: 0.646
Transcripts:
VWF:ENST00000261405.10:c.220+2797del:p.(=)
Pathogenicity Data:
Best Score: 0.646091
REMM: 0.646
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-6055846-C-T [0/1] rs549102454
Variant score: 0.604
Transcripts:
VWF:ENST00000261405.10:c.1945+1011G>A:p.(=)
Pathogenicity Data:
Best Score: 0.609662
REMM: 0.610
Frequency Data:
UK10K: 0.0529%
gnomAD_G_AFR: 0.0073%
gnomAD_G_AMR: 0.0597%
gnomAD_G_EAS: 0.0195%
gnomAD_G_NFE: 0.0457%
gnomAD_G_SAS: 0.0629%
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-6057311-A-ATTTTTTTTTTC [0/1] rs1555198303
Variant score: 0.521
Transcripts:
VWF:ENST00000261405.10:c.1730-240_1730-239insGAAAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.522107
REMM: 0.522
Frequency Data:
gnomAD_G_AFR: 0.0092%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-6020023-T-C [0/1] rs138090017
Variant score: 0.506
Transcripts:
VWF:ENST00000261405.10:c.3675-280A>G:p.(=)
Pathogenicity Data:
Best Score: 0.693225
REMM: 0.693
Frequency Data:
UK10K: 0.4893%
gnomAD_G_AFR: 0.1154%
gnomAD_G_AMR: 0.8365%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.6968%
gnomAD_G_SAS: 1.0969%
MISSENSE_VARIANT SNV 12-6019726-T-G [0|1] rs61749368
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:1, LB:4, B:1)
Variant score: 0.377
Transcripts:
VWF:ENST00000261405.10:c.3692A>C:p.(Asn1231Thr)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 1.0578%
gnomAD_E_AMR: 0.0764%
gnomAD_E_EAS: 0.0655%
gnomAD_E_NFE: 0.1337%
gnomAD_E_SAS: 0.6072%
gnomAD_G_AFR: 1.3197%
gnomAD_G_AMR: 0.1242%
gnomAD_G_EAS: 0.1741%
gnomAD_G_NFE: 0.1912%
gnomAD_G_SAS: 0.9148%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-6087376-T-G [0/1] rs11611549
Variant score: 0.332
Transcripts:
VWF:ENST00000261405.10:c.657+8084A>C:p.(=)
Pathogenicity Data:
Best Score: 0.331956
REMM: 0.332
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 12-6019732-A-C [0|1] rs61749367
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:4, LB:2, B:3)
Variant score: 0.195
Transcripts:
VWF:ENST00000261405.10:c.3686T>G:p.(Val1229Gly)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.0529%
gnomAD_E_AFR: 1.3723%
gnomAD_E_AMR: 0.1078%
gnomAD_E_EAS: 0.0731%
gnomAD_E_NFE: 0.1286%
gnomAD_E_SAS: 0.5155%
gnomAD_G_AFR: 1.7899%
gnomAD_G_AMR: 0.2549%
gnomAD_G_EAS: 0.1736%
gnomAD_G_NFE: 0.1867%
gnomAD_G_SAS: 0.8710%
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-6108334-T-TACACACACACAC [0/1] rs34140032
Variant score: 0.195
Transcripts:
VWF:ENST00000261405.10:c.532+2039_532+2040insGTGTGTGTGTGT:p.(=)
Pathogenicity Data:
Best Score: 0.194814
REMM: 0.195
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-5980212-TAGGG-T [0/1]
Variant score: 0.150
Transcripts:
VWF:ENST00000261405.10:c.7287+1570_7287+1573del:p.(=)
Pathogenicity Data:
Best Score: 0.14993
REMM: 0.150
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-6092614-TGA-T [1/1] rs1555073700
Variant score: 0.074
Transcripts:
VWF:ENST00000261405.10:c.657+2844_657+2845del:p.(=)
Pathogenicity Data:
Best Score: 0.225893
REMM: 0.226
Frequency Data:
gnomAD_G_AFR: 0.7586%
gnomAD_G_AMR: 1.7878%
gnomAD_G_EAS: 1.1307%
gnomAD_G_NFE: 1.1857%
gnomAD_G_SAS: 1.3472%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-6103366-A-G [0/1] rs564596871
Variant score: 0.064
Transcripts:
VWF:ENST00000261405.10:c.532+7008T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0803952
REMM: 0.080
Frequency Data:
gnomAD_G_AFR: 0.9061%
gnomAD_G_AMR: 0.1650%
gnomAD_G_EAS: 0.1583%
gnomAD_G_NFE: 0.0661%
gnomAD_G_SAS: 0.2981%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-5998490-AAAAAAAAAATATATATAT-A [0/1]
Variant score: 0.055
Transcripts:
VWF:ENST00000261405.10:c.5843-2286_5843-2269del:p.(=)
Pathogenicity Data:
Best Score: 0.0547175
REMM: 0.055
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-5998500-T-A [0/1]
Variant score: 0.036
Transcripts:
VWF:ENST00000261405.10:c.5843-2278A>T:p.(=)
Pathogenicity Data:
Best Score: 0.0360766
REMM: 0.036
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-6029027-A-G [0/1]
Variant score: 0.035
Transcripts:
VWF:ENST00000261405.10:c.2967+315T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0352052
REMM: 0.035
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-5980257-T-TAGGGAGGGAGGG [0/1]
Variant score: 0.021
Transcripts:
VWF:ENST00000261405.10:c.7287+1528_7287+1529insCCCTCCCTCCCT:p.(=)
Pathogenicity Data:
Best Score: 0.0210603
REMM: 0.021
Frequency Data:
No frequency data

B4GALT1

Exomiser Score: 0.497 (p=9.1E-2)

Phenotype Score: 0.643

Variant Score: 0.718

Phenotype matches:
Phenotypic similarity 0.643 to B4GALT1-CDG associated with B4GALT1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Phenotypic similarity 0.258 to mouse mutant involving B4GALT1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002416, abnormal proerythroblast morphology
HP:0006625, Multifocal breast carcinoma - MP:0002416, abnormal proerythroblast morphology
Known diseases:
OMIM:607091 Congenital disorder of glycosylation, type IId - autosomal recessive
OMIM:620364 Combined low LDL and fibrinogen - autosomal recessive
ORPHA:79332 B4GALT1-CDG - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.497 (p=9.1E-2)

Phenotype Score: 0.643

Variant Score: 0.718

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.643 to ORPHA:79332 B4GALT1-CDG
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-33130512-C-T [0/1] rs377061045
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting, PP4]
Variant score: 0.847 CONTRIBUTING VARIANT
Transcripts:
B4GALT1:ENST00000379731.5:c.648+4677G>A:p.(=)
Pathogenicity Data:
Best Score: 0.846573
REMM: 0.847
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 9-33157121-T-TACACACACACACACACAC [0/1] rs199541947
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PP4]
Variant score: 0.590 CONTRIBUTING VARIANT
Transcripts:
B4GALT1:ENST00000379731.5:c.412+9636_412+9637insGTGTGTGTGTGTGTGTGT:p.(=)
Pathogenicity Data:
Best Score: 0.808154
REMM: 0.808
Frequency Data:
gnomAD_G_AFR: 1.0968%
gnomAD_G_AMR: 0.1224%
gnomAD_G_EAS: 0.1960%
gnomAD_G_NFE: 0.1484%
gnomAD_G_SAS: 0.1265%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.015 (p=4.3E-1)

Phenotype Score: 0.129

Variant Score: 0.847

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-33130512-C-T [0/1] rs377061045
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.847 CONTRIBUTING VARIANT
Transcripts:
B4GALT1:ENST00000379731.5:c.648+4677G>A:p.(=)
Pathogenicity Data:
Best Score: 0.846573
REMM: 0.847
Frequency Data:
No frequency data
Other passed variants:
THREE_PRIME_UTR_EXON_VARIANT SNV 9-33111285-G-A [0/1] rs759484311
Variant score: 0.002
Transcripts:
B4GALT1:ENST00000379731.5:c.*2169C>T:p.(=)
Pathogenicity Data:
Best Score: 0.002
REMM: 0.002
Frequency Data:
No frequency data

DNAH11

Exomiser Score: 0.490 (p=9.3E-2)

Phenotype Score: 0.554

Variant Score: 0.816

Phenotype matches:
Phenotypic similarity 0.554 to mouse mutant involving DNAH11.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0004733, abnormal thoracic cavity morphology
HP:0006625, Multifocal breast carcinoma - MP:0004733, abnormal thoracic cavity morphology
Proximity score 0.501 in interactome to FSHR and phenotypic similarity 0.676 to 46,XX gonadal dysgenesis associated with FSHR.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
HP:0006625, Multifocal breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
Proximity score 0.501 in interactome to FSHR and phenotypic similarity 0.368 to mouse mutant of FSHR.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000160, kyphosis
HP:0006625, Multifocal breast carcinoma - MP:0000160, kyphosis
Known diseases:
OMIM:611884 Ciliary dyskinesia, primary, 7, with or without situs inversus - autosomal recessive
ORPHA:244 Primary ciliary dyskinesia - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.490 (p=9.3E-2)

Phenotype Score: 0.554

Variant Score: 0.816

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-21718349-A-G [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.951 CONTRIBUTING VARIANT
Transcripts:
DNAH11:ENST00000409508.8:c.7134+424A>G:p.(=)
Pathogenicity Data:
Best Score: 0.951171
REMM: 0.951
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-21813590-G-A [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.681 CONTRIBUTING VARIANT
Transcripts:
DNAH11:ENST00000409508.8:c.10333-2877G>A:p.(=)
Pathogenicity Data:
Best Score: 0.680525
REMM: 0.681
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.158 (p=2.2E-1)

Phenotype Score: 0.277

Variant Score: 0.951

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-21718349-A-G [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.951 CONTRIBUTING VARIANT
Transcripts:
DNAH11:ENST00000409508.8:c.7134+424A>G:p.(=)
Pathogenicity Data:
Best Score: 0.951171
REMM: 0.951
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-21714125-T-C [0/1] rs181796608
Variant score: 0.555
Transcripts:
DNAH11:ENST00000409508.8:c.6983+2265T>C:p.(=)
Pathogenicity Data:
Best Score: 0.595381
REMM: 0.595
Frequency Data:
UK10K: 0.4099%
gnomAD_G_AFR: 0.0769%
gnomAD_G_AMR: 0.3464%
gnomAD_G_NFE: 0.3939%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-21729717-C-CTT [0|1] rs757083343
Variant score: 0.544
Transcripts:
DNAH11:ENST00000409508.8:c.7440+3733_7440+3734insTT:p.(=)
Pathogenicity Data:
Best Score: 0.544162
REMM: 0.544
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-21885169-T-TGTAAA [0/1]
Variant score: 0.475
Transcripts:
DNAH11:ENST00000409508.8:c.12507+759_12507+760insGTAAA:p.(=)
Pathogenicity Data:
Best Score: 0.475097
REMM: 0.475
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-21885169-T-TGTAAAAA [0/1]
Variant score: 0.475
Transcripts:
DNAH11:ENST00000409508.8:c.12507+759_12507+760insGTAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.475097
REMM: 0.475
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 7-21526419-T-C [0/1]
Variant score: 0.471
Transcripts:
DNAH11:ENST00000409508.8::
Pathogenicity Data:
Best Score: 0.471387
REMM: 0.471
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-21588977-G-A [0/1] rs773423224
Variant score: 0.471
Transcripts:
DNAH11:ENST00000409508.8:c.1974-231G>A:p.(=)
Pathogenicity Data:
Best Score: 0.472436
REMM: 0.472
Frequency Data:
UK10K: 0.0264%
gnomAD_G_AFR: 0.0097%
gnomAD_G_AMR: 0.0263%
gnomAD_G_NFE: 0.0191%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-21666663-A-G [0/1] rs1392467354
Variant score: 0.469
Transcripts:
DNAH11:ENST00000409508.8:c.5328+7632A>G:p.(=)
Pathogenicity Data:
Best Score: 0.470229
REMM: 0.470
Frequency Data:
gnomAD_G_EAS: 0.0193%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-21833327-A-C [0|1]
Variant score: 0.448
Transcripts:
DNAH11:ENST00000409508.8:c.10692-9217A>C:p.(=)
Pathogenicity Data:
Best Score: 0.44816
REMM: 0.448
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-21822957-CTTTTTTT-C [1/1]
Variant score: 0.334
Transcripts:
DNAH11:ENST00000409508.8:c.10691+4619_10691+4625del:p.(=)
Pathogenicity Data:
Best Score: 0.333759
REMM: 0.334
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-21877874-CA-C [1/1]
Variant score: 0.253
Transcripts:
DNAH11:ENST00000409508.8:c.12196-2827del:p.(=)
Pathogenicity Data:
Best Score: 0.252791
REMM: 0.253
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-21850364-A-AAAAAAG [0/1] rs1370371869
Variant score: 0.244
Transcripts:
DNAH11:ENST00000409508.8:c.10897-2103_10897-2102insAAAAAG:p.(=)
Pathogenicity Data:
Best Score: 0.244503
REMM: 0.245
Frequency Data:
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0066%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-21626745-CTT-C [1/1] rs34136253
Variant score: 0.201
Transcripts:
DNAH11:ENST00000409508.8:c.4500+6668_4500+6669del:p.(=)
Pathogenicity Data:
Best Score: 0.201466
REMM: 0.201
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-21728237-CTTTTTTTTTTTTTTTT-C [0/1] rs71026816
Variant score: 0.198
Transcripts:
DNAH11:ENST00000409508.8:c.7440+2254_7440+2269del:p.(=)
Pathogenicity Data:
Best Score: 0.198157
REMM: 0.198
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-21728237-CTTTTTTTTT-C [0/1] rs71026816
Variant score: 0.111
Transcripts:
DNAH11:ENST00000409508.8:c.7440+2254_7440+2262del:p.(=)
Pathogenicity Data:
Best Score: 0.11128
REMM: 0.111
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-21789808-T-TC [0/1]
Variant score: 0.088
Transcripts:
DNAH11:ENST00000409508.8:c.10026+466_10026+467insC:p.(=)
Pathogenicity Data:
Best Score: 0.0883675
REMM: 0.088
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-21789808-T-TCTTTTTTCTTTC [0/1]
Variant score: 0.088
Transcripts:
DNAH11:ENST00000409508.8:c.10026+466_10026+467insCTTTTTTCTTTC:p.(=)
Pathogenicity Data:
Best Score: 0.0883675
REMM: 0.088
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-21594063-T-TACAC [1/1] rs59727118
Variant score: 0.036
Transcripts:
DNAH11:ENST00000409508.8:c.2667+2486_2667+2487insACAC:p.(=)
Pathogenicity Data:
Best Score: 0.0362655
REMM: 0.036
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-21726860-CAAAAAA-C [1/1]
Variant score: 0.017
Transcripts:
DNAH11:ENST00000409508.8:c.7440+877_7440+882del:p.(=)
Pathogenicity Data:
Best Score: 0.017354
REMM: 0.017
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-21724777-T-TCACTGGGCCAGGTCATCCTATGAATGTAGGAGTCACTGGGCCAGGTCATCCTATGAATGTAGGAGTCACTGGGCCAGGTCATCCTATGAATATAGGGGA [0|1]
Variant score: 0.012
Transcripts:
DNAH11:ENST00000409508.8:c.7267-1034_7267-1033insCACTGGGCCAGGTCATCCTATGAATGTAGGAGTCACTGGGCCAGGTCATCCTATGAATGTAGGAGTCACTGGGCCAGGTCATCCTATGAATATAGGGGA:p.(=)
Pathogenicity Data:
Best Score: 0.0115687
REMM: 0.012
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-21860369-A-G [0/1] rs949997550
Variant score: 0.001
Transcripts:
DNAH11:ENST00000409508.8:c.11203-1484A>G:p.(=)
Pathogenicity Data:
Best Score: 9.16667E-4
REMM: 0.001
Frequency Data:
gnomAD_G_AMR: 0.0065%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-21880612-A-C [0/1] rs73077555
Variant score: 0.000
Transcripts:
DNAH11:ENST00000409508.8:c.12196-90A>C:p.(=)
Pathogenicity Data:
Best Score: 3.33333E-4
REMM: 0.000
Frequency Data:
UK10K: 0.6083%
gnomAD_E_AFR: 0.0604%
gnomAD_E_AMR: 0.2375%
gnomAD_E_EAS: 0.0052%
gnomAD_E_NFE: 0.4956%
gnomAD_E_SAS: 1.3519%
gnomAD_G_AFR: 0.0866%
gnomAD_G_AMR: 0.3725%
gnomAD_G_EAS: 0.0386%
gnomAD_G_NFE: 0.4292%
gnomAD_G_SAS: 1.7798%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-21781557-C-T [0/1] rs188111443
Variant score: 0.000
Transcripts:
DNAH11:ENST00000409508.8:c.9483+2453C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.2116%
gnomAD_G_AFR: 0.0313%
gnomAD_G_AMR: 0.1177%
gnomAD_G_NFE: 0.1573%
gnomAD_G_SAS: 0.0415%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-21833326-C-T [0|1] rs1029289840
Variant score: 0.000
Transcripts:
DNAH11:ENST00000409508.8:c.10692-9218C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0024%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-21848623-C-T [0/1] rs953038431
Variant score: 0.000
Transcripts:
DNAH11:ENST00000409508.8:c.10897-3844C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0097%
gnomAD_G_NFE: 0.0029%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-21885189-C-A [1|1]
Variant score: 0.000
Transcripts:
DNAH11:ENST00000409508.8:c.12507+779C>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-21885191-C-A [1|1] rs76382993
Variant score: 0.000
Transcripts:
DNAH11:ENST00000409508.8:c.12507+781C>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-21892941-G-T [0|1]
Variant score: 0.000
Transcripts:
DNAH11:ENST00000409508.8:c.12750+274G>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data

UNC5B

Exomiser Score: 0.451 (p=1.1E-1)

Phenotype Score: 0.532

Variant Score: 0.823

Phenotype matches:
Proximity score 0.532 in interactome to FLRT3 and phenotypic similarity 0.620 to Kallmann syndrome associated with FLRT3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003187, Breast hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0003187, Breast hypoplasia
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.451 (p=1.1E-1)

Phenotype Score: 0.532

Variant Score: 0.823

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-71244739-G-A [0/1] rs900526634
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.823 CONTRIBUTING VARIANT
Transcripts:
UNC5B:ENST00000335350.10:c.79+31675G>A:p.(=)
Pathogenicity Data:
Best Score: 0.823198
REMM: 0.823
Frequency Data:
gnomAD_G_NFE: 0.0015%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.252 (p=1.7E-1)

Phenotype Score: 0.532

Variant Score: 0.726

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-71244739-G-A [0/1] rs900526634
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.823 CONTRIBUTING VARIANT
Transcripts:
UNC5B:ENST00000335350.10:c.79+31675G>A:p.(=)
Pathogenicity Data:
Best Score: 0.823198
REMM: 0.823
Frequency Data:
gnomAD_G_NFE: 0.0015%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-71246607-G-A [0/1] rs181224347
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.629 CONTRIBUTING VARIANT
Transcripts:
UNC5B:ENST00000335350.10:c.80-33214G>A:p.(=)
Pathogenicity Data:
Best Score: 0.766201
REMM: 0.766
Frequency Data:
UK10K: 0.5025%
gnomAD_G_AFR: 0.1469%
gnomAD_G_AMR: 0.6149%
gnomAD_G_NFE: 0.8426%
gnomAD_G_SAS: 0.3108%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 10-71270340-AAGGG-A [0/1] rs776665500
Variant score: 0.607
Transcripts:
UNC5B:ENST00000335350.10:c.80-9480_80-9477del:p.(=)
Pathogenicity Data:
Best Score: 0.607271
REMM: 0.607
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 10-71270340-AAGGGAGGG-A [0/1] rs776665500
Variant score: 0.607
Transcripts:
UNC5B:ENST00000335350.10:c.80-9480_80-9473del:p.(=)
Pathogenicity Data:
Best Score: 0.607271
REMM: 0.607
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 10-71292488-A-G [0/1] rs111345852
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.596
Transcripts:
UNC5B:ENST00000335350.10:c.1706A>G:p.(Asn569Ser)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 0.0120%
gnomAD_E_AMR: 0.0278%
gnomAD_E_EAS: 0.0253%
gnomAD_E_NFE: 0.0071%
gnomAD_E_SAS: 0.0192%
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0458%
gnomAD_G_NFE: 0.0088%
INTERGENIC_VARIANT INS 10-71194688-C-CAA [0/1] rs565502306
Variant score: 0.255
Transcripts:
UNC5B:ENST00000335350.10::
Pathogenicity Data:
Best Score: 0.25967
REMM: 0.260
Frequency Data:
gnomAD_G_AFR: 0.0224%
gnomAD_G_AMR: 0.1219%
gnomAD_G_NFE: 0.0528%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-71277609-G-T [0/1] rs150697822
Variant score: 0.001
Transcripts:
UNC5B:ENST00000335350.10:c.80-2212G>T:p.(=)
Pathogenicity Data:
Best Score: 0.00248333
REMM: 0.002
Frequency Data:
UK10K: 0.4761%
gnomAD_G_AFR: 0.0625%
gnomAD_G_AMR: 0.2939%
gnomAD_G_NFE: 0.3955%
gnomAD_G_SAS: 1.3877%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-71251758-C-G [0/1] rs141483769
Variant score: 0.000
Transcripts:
UNC5B:ENST00000335350.10:c.80-28063C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.1851%
gnomAD_G_AFR: 0.0481%
gnomAD_G_AMR: 0.1831%
gnomAD_G_NFE: 0.3454%
gnomAD_G_SAS: 0.6625%

KCNU1

Exomiser Score: 0.435 (p=1.1E-1)

Phenotype Score: 0.501

Variant Score: 0.851

Phenotype matches:
Proximity score 0.501 in interactome to CACNA1C and phenotypic similarity 0.643 to Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures associated with CACNA1C.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Proximity score 0.501 in interactome to CACNA1C and phenotypic similarity 0.349 to mouse mutant of CACNA1C.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002759, abnormal caudal vertebrae morphology
HP:0006625, Multifocal breast carcinoma - MP:0002759, abnormal caudal vertebrae morphology
Proximity score 0.501 in interactome to CACNA1C and phenotypic similarity 0.255 to fish mutant of CACNA1C.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0001052, mandibular arch skeleton morphology, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0001052, mandibular arch skeleton morphology, abnormal
Known diseases:
OMIM:620196 Spermatogenic failure 79 - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.435 (p=1.1E-1)

Phenotype Score: 0.501

Variant Score: 0.851

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-36901735-G-A [0/1] rs149251381
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.901 CONTRIBUTING VARIANT
Transcripts:
KCNU1:ENST00000399881.8:c.2010-3973G>A:p.(=)
Pathogenicity Data:
Best Score: 0.904214
REMM: 0.904
Frequency Data:
gnomAD_G_AMR: 0.0131%
gnomAD_G_NFE: 0.0235%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-36857108-T-A [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.801 CONTRIBUTING VARIANT
Transcripts:
KCNU1:ENST00000399881.8:c.1892-7296T>A:p.(=)
Pathogenicity Data:
Best Score: 0.800579
REMM: 0.801
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.083 (p=2.8E-1)

Phenotype Score: 0.251

Variant Score: 0.901

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-36901735-G-A [0/1] rs149251381
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.901 CONTRIBUTING VARIANT
Transcripts:
KCNU1:ENST00000399881.8:c.2010-3973G>A:p.(=)
Pathogenicity Data:
Best Score: 0.904214
REMM: 0.904
Frequency Data:
gnomAD_G_AMR: 0.0131%
gnomAD_G_NFE: 0.0235%
Other passed variants:
MISSENSE_VARIANT SNV 8-36817717-G-A [0/1] rs200060902
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.596
Transcripts:
KCNU1:ENST00000399881.8:c.1063G>A:p.(Asp355Asn)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.0397%
gnomAD_E_AFR: 0.0090%
gnomAD_E_AMR: 0.0022%
gnomAD_E_NFE: 0.0482%
gnomAD_G_AFR: 0.0098%
gnomAD_G_EAS: 0.0198%
gnomAD_G_NFE: 0.0325%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-36814114-T-C [0/1] rs1020611292
Variant score: 0.478
Transcripts:
KCNU1:ENST00000399881.8:c.733-93T>C:p.(=)
Pathogenicity Data:
Best Score: 0.480227
REMM: 0.480
Frequency Data:
gnomAD_E_AMR: 0.0273%
gnomAD_E_NFE: 0.0243%
gnomAD_E_SAS: 0.0037%
gnomAD_G_AFR: 0.0072%
gnomAD_G_AMR: 0.0196%
gnomAD_G_NFE: 0.0353%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-36854281-T-C [0/1] rs186708341
Variant score: 0.374
Transcripts:
KCNU1:ENST00000399881.8:c.1891+8382T>C:p.(=)
Pathogenicity Data:
Best Score: 0.403434
REMM: 0.403
Frequency Data:
UK10K: 0.2380%
gnomAD_G_AFR: 0.0770%
gnomAD_G_AMR: 0.1177%
gnomAD_G_NFE: 0.4339%
gnomAD_G_SAS: 0.1656%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-36825447-A-G [0/1] rs941127227
Variant score: 0.344
Transcripts:
KCNU1:ENST00000399881.8:c.1106+7687A>G:p.(=)
Pathogenicity Data:
Best Score: 0.345351
REMM: 0.345
Frequency Data:
gnomAD_G_AMR: 0.0131%
gnomAD_G_NFE: 0.0191%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-36890782-T-C [0/1]
Variant score: 0.341
Transcripts:
KCNU1:ENST00000399881.8:c.2010-14926T>C:p.(=)
Pathogenicity Data:
Best Score: 0.341156
REMM: 0.341
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-36907190-G-A [0/1] rs186052360
Variant score: 0.022
Transcripts:
KCNU1:ENST00000399881.8:c.2106+1386G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0223746
REMM: 0.022
Frequency Data:
gnomAD_G_AFR: 0.0337%
gnomAD_G_AMR: 0.0458%
gnomAD_G_NFE: 0.0942%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-36914607-G-C [0/1] rs938658364
Variant score: 0.001
Transcripts:
KCNU1:ENST00000399881.8:c.2521+3488G>C:p.(=)
Pathogenicity Data:
Best Score: 0.001
REMM: 0.001
Frequency Data:
gnomAD_G_NFE: 0.0029%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-36865773-CA-C [0/1]
Variant score: 0.001
Transcripts:
KCNU1:ENST00000399881.8:c.2009+1253del:p.(=)
Pathogenicity Data:
Best Score: 9.61905E-4
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-36797828-C-G [0/1] rs926416305
Variant score: 0.000
Transcripts:
KCNU1:ENST00000399881.8:c.316-6199C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AMR: 0.0131%
gnomAD_G_NFE: 0.0191%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-36843664-C-T [0/1] rs1265832102
Variant score: 0.000
Transcripts:
KCNU1:ENST00000399881.8:c.1704-1916C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_NFE: 0.0015%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-36932023-G-A [0/1] rs963269648
Variant score: 0.000
Transcripts:
KCNU1:ENST00000399881.8:c.2931+878G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AMR: 0.0131%
gnomAD_G_NFE: 0.0191%

ACVR2B

Exomiser Score: 0.419 (p=1.2E-1)

Phenotype Score: 0.503

Variant Score: 0.842

Phenotype matches:
Phenotypic similarity 0.366 to mouse mutant involving ACVR2B.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000150, abnormal rib morphology
HP:0006625, Multifocal breast carcinoma - MP:0000150, abnormal rib morphology
Phenotypic similarity 0.261 to zebrafish mutant involving ACVR2B.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0009685, endochondral bone aplastic, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0009685, endochondral bone aplastic, abnormal
Proximity score 0.503 in interactome to BMP6 and phenotypic similarity 0.614 to Symptomatic form of HFE-related hemochromatosis associated with BMP6.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Proximity score 0.503 in interactome to BMP6 and phenotypic similarity 0.372 to mouse mutant of BMP6.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0004174, abnormal spine curvature
HP:0006625, Multifocal breast carcinoma - MP:0004174, abnormal spine curvature
Known diseases:
OMIM:613751 Heterotaxy, visceral, 4, autosomal - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.419 (p=1.2E-1)

Phenotype Score: 0.503

Variant Score: 0.842

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-38471439-C-T [0|1] rs1287273645
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.842 CONTRIBUTING VARIANT
Transcripts:
ACVR2B:ENST00000352511.5:c.53-5848C>T:p.(=)
Pathogenicity Data:
Best Score: 0.842456
REMM: 0.842
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.032 (p=3.6E-1)

Phenotype Score: 0.251

Variant Score: 0.791

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-38471439-C-T [0|1] rs1287273645
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.842 CONTRIBUTING VARIANT
Transcripts:
ACVR2B:ENST00000352511.5:c.53-5848C>T:p.(=)
Pathogenicity Data:
Best Score: 0.842456
REMM: 0.842
Frequency Data:
No frequency data
THREE_PRIME_UTR_EXON_VARIANT DEL 3-38492731-TACACACACACACACACACACACACACACACACACACACACACAC-T [0/1] rs55986551
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.740 CONTRIBUTING VARIANT
Transcripts:
ACVR2B:ENST00000352511.5:c.*9429_*9472del:p.(=)
Pathogenicity Data:
Best Score: 0.740418
REMM: 0.740
Frequency Data:
No frequency data

ACOX1

Exomiser Score: 0.415 (p=1.2E-1)

Phenotype Score: 0.643

Variant Score: 0.682

Phenotype matches:
Phenotypic similarity 0.643 to Peroxisomal acyl-CoA oxidase deficiency associated with ACOX1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Known diseases:
OMIM:264470 Peroxisomal acyl-CoA oxidase deficiency - autosomal recessive
OMIM:618960 Mitchell syndrome - autosomal dominant
ORPHA:2971 Peroxisomal acyl-CoA oxidase deficiency - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.415 (p=1.2E-1)

Phenotype Score: 0.643

Variant Score: 0.682

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.643 to OMIM:264470 Peroxisomal acyl-CoA oxidase deficiency
Variants contributing to score:
FIVE_PRIME_UTR_EXON_VARIANT SNV 17-75979149-G-C [0/1] rs552785255
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PP4]
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.723 CONTRIBUTING VARIANT
Transcripts:
ACOX1:ENST00000293217.10:c.-76C>G:p.(=)
Pathogenicity Data:
Best Score: 0.746783
REMM: 0.747
Frequency Data:
UK10K: 0.0661%
gnomAD_E_AFR: 0.1386%
gnomAD_E_AMR: 0.1372%
gnomAD_E_NFE: 0.0680%
gnomAD_E_SAS: 0.0954%
gnomAD_G_AFR: 0.0361%
gnomAD_G_AMR: 0.2092%
gnomAD_G_NFE: 0.0809%
gnomAD_G_SAS: 0.1243%
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-75970184-C-CAAAAAAAAAAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting, PP4]
Variant score: 0.641 CONTRIBUTING VARIANT
Transcripts:
ACOX1:ENST00000293217.10:c.269+8349_269+8350insTTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.640655
REMM: 0.641
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.001 (p=7.7E-1)

Phenotype Score: 0.000

Variant Score: 0.641

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-75970184-C-CAAAAAAAAAAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.641 CONTRIBUTING VARIANT
Transcripts:
ACOX1:ENST00000293217.10:c.269+8349_269+8350insTTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.640655
REMM: 0.641
Frequency Data:
No frequency data
Other passed variants:
THREE_PRIME_UTR_EXON_VARIANT DEL 17-75942429-CA-C [0/1]
Variant score: 0.461
Transcripts:
ACOX1:ENST00000293217.10:c.*4318del:p.(=)
Pathogenicity Data:
Best Score: 0.461417
REMM: 0.461
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-75961164-A-G [0/1] rs142148630
Variant score: 0.247
Transcripts:
ACOX1:ENST00000293217.10:c.270-789T>C:p.(=)
Pathogenicity Data:
Best Score: 0.274656
REMM: 0.275
Frequency Data:
UK10K: 0.4761%
gnomAD_G_AFR: 0.1120%
gnomAD_G_AMR: 0.4709%
gnomAD_G_NFE: 0.5566%
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-75968435-C-CAAAAAAAAAAA [0/1]
Variant score: 0.118
Transcripts:
ACOX1:ENST00000293217.10:c.270-8061_270-8060insTTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.117618
REMM: 0.118
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-75970613-A-G [0/1]
Variant score: 0.043
Transcripts:
ACOX1:ENST00000293217.10:c.269+7921T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0427171
REMM: 0.043
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 17-75956945-CTCTCTCTCTCTCTCTCTCTCTCTCTCTATATATA-C [0/1] rs1567877798
Variant score: 0.021
Transcripts:
ACOX1:ENST00000293217.10:c.538+480_538+513del:p.(=)
Pathogenicity Data:
Best Score: 0.0228599
REMM: 0.023
Frequency Data:
gnomAD_G_AFR: 0.5358%
gnomAD_G_AMR: 0.1701%
gnomAD_G_EAS: 0.0865%
gnomAD_G_NFE: 0.0274%
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-75956971-C-CTATA [0/1]
Variant score: 0.016
Transcripts:
ACOX1:ENST00000293217.10:c.538+487_538+488insTATA:p.(=)
Pathogenicity Data:
Best Score: 0.0155361
REMM: 0.016
Frequency Data:
No frequency data
THREE_PRIME_UTR_EXON_VARIANT SNV 17-75944481-T-C [0/1] rs541192594
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.005
Transcripts:
ACOX1:ENST00000293217.10:c.*2267A>G:p.(=)
Pathogenicity Data:
Best Score: 0.00524444
REMM: 0.005
Frequency Data:
UK10K: 0.0793%
gnomAD_G_AFR: 0.0313%
gnomAD_G_AMR: 0.1700%
gnomAD_G_NFE: 0.0750%
gnomAD_G_SAS: 0.1244%

CYP7B1

Exomiser Score: 0.409 (p=1.2E-1)

Phenotype Score: 0.505

Variant Score: 0.835

Phenotype matches:
Proximity score 0.505 in interactome to CYP11A1 and phenotypic similarity 0.614 to 46,XY difference of sex development-adrenal insufficiency due to CYP11A1 deficiency associated with CYP11A1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Known diseases:
OMIM:270800 Spastic paraplegia 5A, autosomal recessive - autosomal recessive
OMIM:613812 Bile acid synthesis defect, congenital, 3 - autosomal recessive
ORPHA:100986 Autosomal recessive spastic paraplegia type 5A - autosomal recessive
ORPHA:79302 Congenital bile acid synthesis defect type 3 - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.409 (p=1.2E-1)

Phenotype Score: 0.505

Variant Score: 0.835

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-64640931-G-A [0/1] rs184997903
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.961 CONTRIBUTING VARIANT
Transcripts:
CYP7B1:ENST00000310193.4:c.123-16392C>T:p.(=)
Pathogenicity Data:
Best Score: 0.990633
REMM: 0.991
Frequency Data:
UK10K: 0.1984%
gnomAD_G_AFR: 0.0217%
gnomAD_G_NFE: 0.1852%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-64598623-G-A [0/1] rs562186929
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.709 CONTRIBUTING VARIANT
Transcripts:
CYP7B1:ENST00000310193.4:c.1234-1694C>T:p.(=)
Pathogenicity Data:
Best Score: 0.772985
REMM: 0.773
Frequency Data:
UK10K: 0.0926%
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.4773%
gnomAD_G_EAS: 0.0386%
gnomAD_G_NFE: 0.0764%
gnomAD_G_SAS: 0.3944%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.001 (p=7.7E-1)

Phenotype Score: 0.253

Variant Score: 0.355

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-64665559-GTTTTTT-G [0/1] rs540578806
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.355 CONTRIBUTING VARIANT
Transcripts:
CYP7B1:ENST00000310193.4:c.123-41026_123-41021del:p.(=)
Pathogenicity Data:
Best Score: 0.354968
REMM: 0.355
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-64771511-AT-A [0/1] rs544591242
Variant score: 0.513
Transcripts:
CYP7B1:ENST00000310193.4:c.122+26954del:p.(=)
Pathogenicity Data:
Best Score: 0.527996
REMM: 0.528
Frequency Data:
UK10K: 0.1851%
gnomAD_G_AFR: 0.0241%
gnomAD_G_NFE: 0.1779%
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-64764229-G-GC [1/1] rs59605103
Variant score: 0.384
Transcripts:
CYP7B1:ENST00000310193.4:c.122+34236_122+34237insG:p.(=)
Pathogenicity Data:
Best Score: 0.38424
REMM: 0.384
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-64624951-CTTTTTTTTTTTTTT-C [0/1] rs71260892
Variant score: 0.311
Transcripts:
CYP7B1:ENST00000310193.4:c.123-426_123-413del:p.(=)
Pathogenicity Data:
Best Score: 0.310672
REMM: 0.311
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-64677438-CAAA-C [0/1]
Variant score: 0.291
Transcripts:
CYP7B1:ENST00000310193.4:c.123-52902_123-52900del:p.(=)
Pathogenicity Data:
Best Score: 0.291415
REMM: 0.291
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-64768360-C-CA [0/1] rs74274932
Variant score: 0.157
Transcripts:
CYP7B1:ENST00000310193.4:c.122+30105_122+30106insT:p.(=)
Pathogenicity Data:
Best Score: 0.156926
REMM: 0.157
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-64745379-G-A [0/1]
Variant score: 0.134
Transcripts:
CYP7B1:ENST00000310193.4:c.122+53087C>T:p.(=)
Pathogenicity Data:
Best Score: 0.134363
REMM: 0.134
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-64686842-T-C [0/1] rs12155709
Variant score: 0.068
Transcripts:
CYP7B1:ENST00000310193.4:c.123-62303A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0682107
REMM: 0.068
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-64665559-G-GT [0/1]
Variant score: 0.006
Transcripts:
CYP7B1:ENST00000310193.4:c.123-41021_123-41020insA:p.(=)
Pathogenicity Data:
Best Score: 0.00555675
REMM: 0.006
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-64643088-T-TATATATATACACATATATATACATATATATACACATATATATAC [0/1] rs1342546171
Variant score: 0.002
Transcripts:
CYP7B1:ENST00000310193.4:c.123-18550_123-18549insGTATATATATGTGTATATATATGTATATATATGTGTATATATAT:p.(=)
Pathogenicity Data:
Best Score: 0.00151667
REMM: 0.002
Frequency Data:
No frequency data

AUTS2

Exomiser Score: 0.408 (p=1.2E-1)

Phenotype Score: 0.502

Variant Score: 0.838

Phenotype matches:
Phenotypic similarity 0.211 to zebrafish mutant involving AUTS2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0005071, Meckel's cartilage decreased distance ceratohyal cartilage, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0005071, Meckel's cartilage decreased distance ceratohyal cartilage, abnormal
Proximity score 0.502 in interactome to DYRK1A and phenotypic similarity 0.618 to DYRK1A-related intellectual disability syndrome due to 21q22.13q22.2 microdeletion associated with DYRK1A.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0100783, Breast aplasia
HP:0006625, Multifocal breast carcinoma - HP:0100783, Breast aplasia
Known diseases:
OMIM:615834 Intellectual developmental disorder, autosomal dominant 26 - autosomal dominant
ORPHA:352490 Autism spectrum disorder due to AUTS2 deficiency - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.408 (p=1.2E-1)

Phenotype Score: 0.502

Variant Score: 0.838

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-70716636-C-CAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.838 CONTRIBUTING VARIANT
Transcripts:
AUTS2:ENST00000342771.10:c.742+18016_742+18017insAA:p.(=)
Pathogenicity Data:
Best Score: 0.837735
REMM: 0.838
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.041 (p=3.4E-1)

Phenotype Score: 0.251

Variant Score: 0.819

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-70716636-C-CAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.838 CONTRIBUTING VARIANT
Transcripts:
AUTS2:ENST00000342771.10:c.742+18016_742+18017insAA:p.(=)
Pathogenicity Data:
Best Score: 0.837735
REMM: 0.838
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70233996-A-G [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.801 CONTRIBUTING VARIANT
Transcripts:
AUTS2:ENST00000342771.10:c.660+99425A>G:p.(=)
Pathogenicity Data:
Best Score: 0.801198
REMM: 0.801
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70598817-T-C [0/1]
Variant score: 0.757
Transcripts:
AUTS2:ENST00000342771.10:c.691-99752T>C:p.(=)
Pathogenicity Data:
Best Score: 0.756746
REMM: 0.757
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-69872834-C-CTT [0/1] rs1164356683
Variant score: 0.738
Transcripts:
AUTS2:ENST00000342771.10:c.310-26452_310-26451insTT:p.(=)
Pathogenicity Data:
Best Score: 0.737998
REMM: 0.738
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-70639616-C-CAAA [0/1]
Variant score: 0.710
Transcripts:
AUTS2:ENST00000342771.10:c.691-58953_691-58952insAAA:p.(=)
Pathogenicity Data:
Best Score: 0.709635
REMM: 0.710
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-70460338-CT-C [0/1]
Variant score: 0.705
Transcripts:
AUTS2:ENST00000342771.10:c.690+24558del:p.(=)
Pathogenicity Data:
Best Score: 0.704625
REMM: 0.705
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-70050510-A-AG [0|1] rs753557140
Variant score: 0.700
Transcripts:
AUTS2:ENST00000342771.10:c.523-67622_523-67621insG:p.(=)
Pathogenicity Data:
Best Score: 0.712496
REMM: 0.712
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.1246%
gnomAD_G_NFE: 0.0632%
gnomAD_G_SAS: 0.0207%
INTERGENIC_VARIANT INS 7-69584740-C-CAAAAAAAA [0/1]
Variant score: 0.608
Transcripts:
AUTS2:ENST00000342771.10::
Pathogenicity Data:
Best Score: 0.608175
REMM: 0.608
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 7-69584740-CA-C [0/1]
Variant score: 0.608
Transcripts:
AUTS2:ENST00000342771.10::
Pathogenicity Data:
Best Score: 0.608175
REMM: 0.608
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70715603-C-G [0/1] rs144563233
Variant score: 0.596
Transcripts:
AUTS2:ENST00000342771.10:c.742+16983C>G:p.(=)
Pathogenicity Data:
Best Score: 0.611292
REMM: 0.611
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AFR: 0.0217%
gnomAD_G_AMR: 0.1706%
gnomAD_G_NFE: 0.0809%
gnomAD_G_SAS: 0.0623%
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-69796523-C-CAA [0/1] rs57474916
Variant score: 0.594
Transcripts:
AUTS2:ENST00000342771.10:c.310-102763_310-102762insAA:p.(=)
Pathogenicity Data:
Best Score: 0.595936
REMM: 0.596
Frequency Data:
gnomAD_G_AFR: 0.0029%
gnomAD_G_NFE: 0.0052%
gnomAD_G_SAS: 0.0253%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-69614371-TAAGAG-T [0|1]
Variant score: 0.564
Transcripts:
AUTS2:ENST00000342771.10:c.309+14410_309+14414del:p.(=)
Pathogenicity Data:
Best Score: 0.563562
REMM: 0.564
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70723262-T-C [0/1] rs190475401
Variant score: 0.561
Transcripts:
AUTS2:ENST00000342771.10:c.742+24642T>C:p.(=)
Pathogenicity Data:
Best Score: 0.592367
REMM: 0.592
Frequency Data:
UK10K: 0.2645%
gnomAD_G_AFR: 0.0433%
gnomAD_G_AMR: 0.3267%
gnomAD_G_NFE: 0.2205%
gnomAD_G_SAS: 0.0414%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70050509-T-A [0|1] rs764020572
Variant score: 0.540
Transcripts:
AUTS2:ENST00000342771.10:c.523-67623T>A:p.(=)
Pathogenicity Data:
Best Score: 0.549651
REMM: 0.550
Frequency Data:
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.1246%
gnomAD_G_NFE: 0.0632%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-69747818-TGA-T [0/1] rs1466059537
Variant score: 0.535
Transcripts:
AUTS2:ENST00000342771.10:c.309+147857_309+147858del:p.(=)
Pathogenicity Data:
Best Score: 0.535002
REMM: 0.535
Frequency Data:
gnomAD_G_AFR: 0.0025%
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-70579244-T-TAAAAAAAAAAAAAA [0/1]
Variant score: 0.514
Transcripts:
AUTS2:ENST00000342771.10:c.691-119325_691-119324insAAAAAAAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.513569
REMM: 0.514
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-70579244-T-TAAAAAAAAAAAAAAAA [0/1]
Variant score: 0.514
Transcripts:
AUTS2:ENST00000342771.10:c.691-119325_691-119324insAAAAAAAAAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.513569
REMM: 0.514
Frequency Data:
No frequency data
DOWNSTREAM_GENE_VARIANT DEL 7-70796445-ATTTTTTTTTTTTTTTTTTTTTT-A [0/1] rs56972625
Variant score: 0.496
Transcripts:
AUTS2:ENST00000342771.10::
Pathogenicity Data:
Best Score: 0.495502
REMM: 0.496
Frequency Data:
No frequency data
DOWNSTREAM_GENE_VARIANT DEL 7-70796445-ATTTTTTTT-A [0/1] rs56972625
Variant score: 0.495
Transcripts:
AUTS2:ENST00000342771.10::
Pathogenicity Data:
Best Score: 0.495502
REMM: 0.496
Frequency Data:
gnomAD_G_AFR: 0.0080%
gnomAD_G_NFE: 0.0035%
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-69996946-T-TAAAAAAAAAAAA [0/1] rs1161825217
Variant score: 0.494
Transcripts:
AUTS2:ENST00000342771.10:c.522+97448_522+97449insAAAAAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.494077
REMM: 0.494
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-70531133-T-TGAGAAATATTTGATCTAGCAAACTGTACTAAGATGAGACATAAATATCTAA [0/1] rs1554422688
Variant score: 0.488
Transcripts:
AUTS2:ENST00000342771.10:c.690+95352_690+95353insGAGAAATATTTGATCTAGCAAACTGTACTAAGATGAGACATAAATATCTAA:p.(=)
Pathogenicity Data:
Best Score: 0.488265
REMM: 0.488
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 7-70810519-ATT-A [1/1] rs71889484
Variant score: 0.473
Transcripts:
AUTS2:ENST00000342771.10::
Pathogenicity Data:
Best Score: 0.472581
REMM: 0.473
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-70163344-T-TGGG [0/1]
Variant score: 0.473
Transcripts:
AUTS2:ENST00000342771.10:c.660+28773_660+28774insGGG:p.(=)
Pathogenicity Data:
Best Score: 0.472525
REMM: 0.473
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-70610423-CTTTT-C [0/1] rs3054735
Variant score: 0.459
Transcripts:
AUTS2:ENST00000342771.10:c.691-88145_691-88142del:p.(=)
Pathogenicity Data:
Best Score: 0.458692
REMM: 0.459
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-70743468-CA-C [0/1]
Variant score: 0.444
Transcripts:
AUTS2:ENST00000342771.10:c.743-19401del:p.(=)
Pathogenicity Data:
Best Score: 0.443945
REMM: 0.444
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-70743468-CAA-C [0/1]
Variant score: 0.444
Transcripts:
AUTS2:ENST00000342771.10:c.743-19401_743-19400del:p.(=)
Pathogenicity Data:
Best Score: 0.443945
REMM: 0.444
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-69614367-T-TCTTTCTTTCTTTCTTTC [0/1]
Variant score: 0.440
Transcripts:
AUTS2:ENST00000342771.10:c.309+14405_309+14406insCTTTCTTTCTTTCTTTC:p.(=)
Pathogenicity Data:
Best Score: 0.439583
REMM: 0.440
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-70162445-CAAAAAAAAAAAAAAA-C [0/1]
Variant score: 0.438
Transcripts:
AUTS2:ENST00000342771.10:c.660+27875_660+27889del:p.(=)
Pathogenicity Data:
Best Score: 0.437785
REMM: 0.438
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-70338833-C-CTTTATTTATTTAT [0/1]
Variant score: 0.390
Transcripts:
AUTS2:ENST00000342771.10:c.661-96919_661-96918insTTTATTTATTTAT:p.(=)
Pathogenicity Data:
Best Score: 0.389554
REMM: 0.390
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-69946557-TACACACAC-T [0/1] rs57891742
Variant score: 0.369
Transcripts:
AUTS2:ENST00000342771.10:c.522+47060_522+47067del:p.(=)
Pathogenicity Data:
Best Score: 0.368785
REMM: 0.369
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-69602034-ATATATATGTGTGTGTGTGTGTGTGTG-A [0|1] rs1439273259
Variant score: 0.346
Transcripts:
AUTS2:ENST00000342771.10:c.309+2073_309+2098del:p.(=)
Pathogenicity Data:
Best Score: 0.34591
REMM: 0.346
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-69978859-AACACACAC-A [0/1] rs71068004
Variant score: 0.326
Transcripts:
AUTS2:ENST00000342771.10:c.522+79362_522+79369del:p.(=)
Pathogenicity Data:
Best Score: 0.326252
REMM: 0.326
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70436954-T-C [0/1] rs35274616
Variant score: 0.291
Transcripts:
AUTS2:ENST00000342771.10:c.690+1173T>C:p.(=)
Pathogenicity Data:
Best Score: 0.990589
REMM: 0.991
Frequency Data:
UK10K: 1.6794%
gnomAD_G_AFR: 0.2861%
gnomAD_G_AMR: 1.5171%
gnomAD_G_NFE: 1.8272%
gnomAD_G_SAS: 1.1397%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-69850398-CAAAAAAA-C [0/1]
Variant score: 0.247
Transcripts:
AUTS2:ENST00000342771.10:c.310-48887_310-48881del:p.(=)
Pathogenicity Data:
Best Score: 0.246773
REMM: 0.247
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70201970-C-G [0/1]
Variant score: 0.226
Transcripts:
AUTS2:ENST00000342771.10:c.660+67399C>G:p.(=)
Pathogenicity Data:
Best Score: 0.22628
REMM: 0.226
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-70156891-TAAAAAA-T [0/1]
Variant score: 0.222
Transcripts:
AUTS2:ENST00000342771.10:c.660+22321_660+22326del:p.(=)
Pathogenicity Data:
Best Score: 0.221889
REMM: 0.222
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-70110859-CTT-C [0/1] rs71077618
Variant score: 0.182
Transcripts:
AUTS2:ENST00000342771.10:c.523-7272_523-7271del:p.(=)
Pathogenicity Data:
Best Score: 0.182338
REMM: 0.182
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-70003477-GAA-G [0/1] rs1236662999
Variant score: 0.141
Transcripts:
AUTS2:ENST00000342771.10:c.522+103980_522+103981del:p.(=)
Pathogenicity Data:
Best Score: 0.142941
REMM: 0.143
Frequency Data:
gnomAD_G_AFR: 0.0822%
gnomAD_G_EAS: 0.0491%
gnomAD_G_SAS: 0.0390%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-70003691-AAT-A [0/1] rs375552691
Variant score: 0.138
Transcripts:
AUTS2:ENST00000342771.10:c.522+104194_522+104195del:p.(=)
Pathogenicity Data:
Best Score: 0.138884
REMM: 0.139
Frequency Data:
gnomAD_G_AFR: 0.0186%
gnomAD_G_EAS: 0.0352%
gnomAD_G_NFE: 0.0073%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-70689775-CA-C [1/1] rs60869776
Variant score: 0.138
Transcripts:
AUTS2:ENST00000342771.10:c.691-8793del:p.(=)
Pathogenicity Data:
Best Score: 0.137515
REMM: 0.138
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-70043547-CCCTTCCTT-C [1/1] rs71068010
Variant score: 0.131
Transcripts:
AUTS2:ENST00000342771.10:c.523-74584_523-74577del:p.(=)
Pathogenicity Data:
Best Score: 0.130537
REMM: 0.131
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70202040-G-A [1/1]
Variant score: 0.124
Transcripts:
AUTS2:ENST00000342771.10:c.660+67469G>A:p.(=)
Pathogenicity Data:
Best Score: 0.124494
REMM: 0.124
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70039092-C-T [0/1] rs13228050
Variant score: 0.115
Transcripts:
AUTS2:ENST00000342771.10:c.523-79040C>T:p.(=)
Pathogenicity Data:
Best Score: 0.478073
REMM: 0.478
Frequency Data:
UK10K: 1.6794%
gnomAD_G_AFR: 0.3332%
gnomAD_G_AMR: 1.4299%
gnomAD_G_NFE: 1.8886%
gnomAD_G_SAS: 1.0824%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-69876344-AAAAAAATATAT-A [0/1] rs1287940979
Variant score: 0.088
Transcripts:
AUTS2:ENST00000342771.10:c.310-22941_310-22931del:p.(=)
Pathogenicity Data:
Best Score: 0.0880492
REMM: 0.088
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-70004170-A-ATTATATATGAATGTGTTATATGTGAATATATATAATATGAATGTGTTATATGTGAATATATATATTAT [0/1] rs1418809654
Variant score: 0.084
Transcripts:
AUTS2:ENST00000342771.10:c.522+104672_522+104673insTTATATATGAATGTGTTATATGTGAATATATATAATATGAATGTGTTATATGTGAATATATATATTAT:p.(=)
Pathogenicity Data:
Best Score: 0.0844425
REMM: 0.084
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70787575-C-T [0/1] rs1202030534
Variant score: 0.078
Transcripts:
AUTS2:ENST00000342771.10:c.2531+144C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0778694
REMM: 0.078
Frequency Data:
gnomAD_E_NFE: 0.0014%
gnomAD_E_SAS: 0.0022%
gnomAD_G_AFR: 0.0024%
gnomAD_G_NFE: 0.0015%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70497044-A-G [0/1] rs13229168
Variant score: 0.064
Transcripts:
AUTS2:ENST00000342771.10:c.690+61263A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0706746
REMM: 0.071
Frequency Data:
gnomAD_G_AFR: 0.5099%
gnomAD_G_AMR: 0.1190%
gnomAD_G_EAS: 0.1793%
gnomAD_G_NFE: 0.2636%
gnomAD_G_SAS: 0.4084%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70313688-C-A [0/1] rs777466591
Variant score: 0.061
Transcripts:
AUTS2:ENST00000342771.10:c.661-122064C>A:p.(=)
Pathogenicity Data:
Best Score: 0.0613246
REMM: 0.061
Frequency Data:
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0916%
gnomAD_G_NFE: 0.0500%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70202674-A-G [0/1] rs377545366
Variant score: 0.043
Transcripts:
AUTS2:ENST00000342771.10:c.660+68103A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0431425
REMM: 0.043
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-70621838-C-CTTT [0/1] rs67123941
Variant score: 0.041
Transcripts:
AUTS2:ENST00000342771.10:c.691-76731_691-76730insTTT:p.(=)
Pathogenicity Data:
Best Score: 0.041106
REMM: 0.041
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70014627-C-T [0/1]
Variant score: 0.021
Transcripts:
AUTS2:ENST00000342771.10:c.523-103505C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0207333
REMM: 0.021
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70202896-C-T [0|1] rs540828468
Variant score: 0.016
Transcripts:
AUTS2:ENST00000342771.10:c.660+68325C>T:p.(=)
Pathogenicity Data:
Best Score: 0.015675
REMM: 0.016
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70630257-A-G [0/1] rs13246814
Variant score: 0.015
Transcripts:
AUTS2:ENST00000342771.10:c.691-68312A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0407575
REMM: 0.041
Frequency Data:
UK10K: 1.6662%
gnomAD_G_AFR: 0.3162%
gnomAD_G_AMR: 1.7413%
gnomAD_G_NFE: 1.6482%
gnomAD_G_SAS: 1.1686%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-69602040-ATGTGTGTGTG-A [0/1] rs6150156
Variant score: 0.014
Transcripts:
AUTS2:ENST00000342771.10:c.309+2079_309+2088del:p.(=)
Pathogenicity Data:
Best Score: 0.0255841
REMM: 0.026
Frequency Data:
gnomAD_G_AFR: 0.4288%
gnomAD_G_AMR: 1.0185%
gnomAD_G_EAS: 1.4925%
gnomAD_G_NFE: 0.5050%
gnomAD_G_SAS: 0.4992%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70497219-G-A [0/1] rs146170547
Variant score: 0.014
Transcripts:
AUTS2:ENST00000342771.10:c.690+61438G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0221278
REMM: 0.022
Frequency Data:
UK10K: 1.3488%
gnomAD_G_AFR: 0.2401%
gnomAD_G_AMR: 1.0044%
gnomAD_G_NFE: 1.2111%
gnomAD_G_SAS: 0.9151%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70202897-A-G [0|1] rs368319618
Variant score: 0.013
Transcripts:
AUTS2:ENST00000342771.10:c.660+68326A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0127583
REMM: 0.013
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70199628-A-G [0/1]
Variant score: 0.013
Transcripts:
AUTS2:ENST00000342771.10:c.660+65057A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0125901
REMM: 0.013
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70004069-T-A [0/1] rs111211653
Variant score: 0.009
Transcripts:
AUTS2:ENST00000342771.10:c.522+104571T>A:p.(=)
Pathogenicity Data:
Best Score: 0.0120504
REMM: 0.012
Frequency Data:
gnomAD_G_AFR: 0.4513%
gnomAD_G_AMR: 0.5077%
gnomAD_G_EAS: 0.3100%
gnomAD_G_NFE: 0.9596%
gnomAD_G_SAS: 0.5160%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70199935-C-G [1/1]
Variant score: 0.007
Transcripts:
AUTS2:ENST00000342771.10:c.660+65364C>G:p.(=)
Pathogenicity Data:
Best Score: 0.00674722
REMM: 0.007
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70200180-T-C [0/1] rs1464179721
Variant score: 0.005
Transcripts:
AUTS2:ENST00000342771.10:c.660+65609T>C:p.(=)
Pathogenicity Data:
Best Score: 0.00538056
REMM: 0.005
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70316869-G-A [0/1] rs776352807
Variant score: 0.005
Transcripts:
AUTS2:ENST00000342771.10:c.661-118883G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00467063
REMM: 0.005
Frequency Data:
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.1112%
gnomAD_G_NFE: 0.0573%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70200440-C-T [0/1] rs1296673247
Variant score: 0.004
Transcripts:
AUTS2:ENST00000342771.10:c.660+65869C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0042377
REMM: 0.004
Frequency Data:
gnomAD_G_AFR: 0.3676%
gnomAD_G_AMR: 0.6944%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70733550-A-C [1|1] rs6965271
Variant score: 0.001
Transcripts:
AUTS2:ENST00000342771.10:c.743-29320A>C:p.(=)
Pathogenicity Data:
Best Score: 0.001
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-69614376-G-GCTTTCTTTTCTTTCTTTCTTTCTTTCTTTCTTTCT [0|1]
Variant score: 0.001
Transcripts:
AUTS2:ENST00000342771.10:c.309+14414_309+14415insCTTTCTTTTCTTTCTTTCTTTCTTTCTTTCTTTCT:p.(=)
Pathogenicity Data:
Best Score: 9.5E-4
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-70605546-C-CT [0/1] rs530551128
Variant score: 0.001
Transcripts:
AUTS2:ENST00000342771.10:c.691-93023_691-93022insT:p.(=)
Pathogenicity Data:
Best Score: 7.5E-4
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-70605546-C-CTT [0/1] rs530551128
Variant score: 0.001
Transcripts:
AUTS2:ENST00000342771.10:c.691-93023_691-93022insTT:p.(=)
Pathogenicity Data:
Best Score: 7.5E-4
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70168926-C-T [0/1] rs1808524472
Variant score: 0.000
Transcripts:
AUTS2:ENST00000342771.10:c.660+34355C>T:p.(=)
Pathogenicity Data:
Best Score: 5.0E-4
REMM: 0.001
Frequency Data:
gnomAD_G_SAS: 0.0209%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70709165-C-G [0/1] rs866118019
Variant score: 0.000
Transcripts:
AUTS2:ENST00000342771.10:c.742+10545C>G:p.(=)
Pathogenicity Data:
Best Score: 1.11111E-4
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0982%
gnomAD_G_NFE: 0.0338%
gnomAD_G_SAS: 0.0208%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70051579-C-T [0/1] rs567412741
Variant score: 0.000
Transcripts:
AUTS2:ENST00000342771.10:c.523-66553C>T:p.(=)
Pathogenicity Data:
Best Score: 1.0E-4
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0169%
gnomAD_G_NFE: 0.0044%
gnomAD_G_SAS: 0.3120%
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-70303434-G-GCGCACACACACACA [0/1] rs1241517255
Variant score: 0.000
Transcripts:
AUTS2:ENST00000342771.10:c.661-132318_661-132317insCGCACACACACACA:p.(=)
Pathogenicity Data:
Best Score: 2.0E-4
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.4413%
gnomAD_G_AMR: 1.8396%
gnomAD_G_EAS: 1.5698%
gnomAD_G_NFE: 1.6083%
gnomAD_G_SAS: 1.2140%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-69786387-C-T [0/1] rs547960938
Variant score: 0.000
Transcripts:
AUTS2:ENST00000342771.10:c.310-112899C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.2242%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.0044%
gnomAD_G_SAS: 0.0832%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-70064490-A-C [0/1]
Variant score: 0.000
Transcripts:
AUTS2:ENST00000342771.10:c.523-53642A>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-70203344-T-TAA [0/1]
Variant score: 0.000
Transcripts:
AUTS2:ENST00000342771.10:c.660+68773_660+68774insAA:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-70222888-CT-C [0/1] rs200649101
Variant score: 0.000
Transcripts:
AUTS2:ENST00000342771.10:c.660+88318del:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 1.4601%
gnomAD_G_AMR: 0.3200%
gnomAD_G_EAS: 0.1976%
gnomAD_G_NFE: 0.2176%
gnomAD_G_SAS: 0.4983%
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-70731420-C-CTT [0/1] rs56244002
Variant score: 0.000
Transcripts:
AUTS2:ENST00000342771.10:c.743-31450_743-31449insTT:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.3004%
gnomAD_G_AMR: 0.3444%
gnomAD_G_EAS: 0.5006%
gnomAD_G_NFE: 0.2269%

FGFR1

Exomiser Score: 0.406 (p=1.2E-1)

Phenotype Score: 0.620

Variant Score: 0.704

Phenotype matches:
Phenotypic similarity 0.620 to Kallmann syndrome associated with FGFR1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003187, Breast hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0003187, Breast hypoplasia
Phenotypic similarity 0.392 to mouse mutant involving FGFR1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002114, abnormal axial skeleton morphology
HP:0006625, Multifocal breast carcinoma - MP:0002114, abnormal axial skeleton morphology
Phenotypic similarity 0.273 to zebrafish mutant involving FGFR1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0009706, scale increased size, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0009706, scale increased size, abnormal
Known diseases:
OMIM:101600 Pfeiffer syndrome - autosomal dominant
OMIM:123150 Jackson-Weiss syndrome - autosomal dominant
OMIM:147950 Hypogonadotropic hypogonadism 2 with or without anosmia - autosomal dominant
OMIM:166250 Osteoglophonic dysplasia - autosomal dominant
OMIM:190440 Trigonocephaly 1 - autosomal dominant
OMIM:613001 Encephalocraniocutaneous lipomatosis, somatic mosaic - somatic
OMIM:615465 Hartsfield syndrome - autosomal dominant
ORPHA:2117 Hartsfield syndrome - autosomal dominant
ORPHA:220386 Semilobar holoprosencephaly - polygenic
ORPHA:2396 Encephalocraniocutaneous lipomatosis (unconfirmed)
ORPHA:2645 Osteoglosphonic dysplasia - autosomal dominant
ORPHA:280200 Microform holoprosencephaly - polygenic
ORPHA:3157 Septo-optic dysplasia spectrum - autosomal dominant/recessive
ORPHA:3366 Non-syndromic metopic craniosynostosis - autosomal dominant
ORPHA:432 Normosmic congenital hypogonadotropic hypogonadism - autosomal dominant
ORPHA:478 Kallmann syndrome - autosomal dominant
ORPHA:93258 Pfeiffer syndrome type 1 - autosomal dominant
ORPHA:93924 Lobar holoprosencephaly - polygenic
ORPHA:99798 Oligodontia - autosomal dominant/recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.406 (p=1.2E-1)

Phenotype Score: 0.620

Variant Score: 0.704

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.620 to ORPHA:478 Kallmann syndrome
Phenotypic similarity 0.616 to ORPHA:432 Normosmic congenital hypogonadotropic hypogonadism
Phenotypic similarity 0.614 to OMIM:147950 Hypogonadotropic hypogonadism 2 with or without anosmia
Phenotypic similarity 0.428 to OMIM:166250 Osteoglophonic dysplasia
Phenotypic similarity 0.380 to ORPHA:2645 Osteoglosphonic dysplasia
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-38422144-C-T [0/1] rs531819597
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PP4]
Variant score: 0.704 CONTRIBUTING VARIANT
Transcripts:
FGFR1:ENST00000447712.7:c.937-203G>A:p.(=)
Pathogenicity Data:
Best Score: 0.707703
REMM: 0.708
Frequency Data:
UK10K: 0.0397%
gnomAD_E_AFR: 0.0077%
gnomAD_E_AMR: 0.0042%
gnomAD_E_EAS: 0.0068%
gnomAD_E_NFE: 0.0320%
gnomAD_E_SAS: 0.0101%
gnomAD_G_AFR: 0.0120%
gnomAD_G_EAS: 0.0386%
gnomAD_G_NFE: 0.0294%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.058 (p=3.1E-1)

Phenotype Score: 0.392

Variant Score: 0.700

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-38422144-C-T [0/1] rs531819597
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.704 CONTRIBUTING VARIANT
Transcripts:
FGFR1:ENST00000447712.7:c.937-203G>A:p.(=)
Pathogenicity Data:
Best Score: 0.707703
REMM: 0.708
Frequency Data:
UK10K: 0.0397%
gnomAD_E_AFR: 0.0077%
gnomAD_E_AMR: 0.0042%
gnomAD_E_EAS: 0.0068%
gnomAD_E_NFE: 0.0320%
gnomAD_E_SAS: 0.0101%
gnomAD_G_AFR: 0.0120%
gnomAD_G_EAS: 0.0386%
gnomAD_G_NFE: 0.0294%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-38447098-AACAC-A [0/1] rs57917657
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.696 CONTRIBUTING VARIANT
Transcripts:
FGFR1:ENST00000447712.7:c.91+10254_91+10257del:p.(=)
Pathogenicity Data:
Best Score: 0.696048
REMM: 0.696
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-38444051-CA-C [0/1]
Variant score: 0.628
Transcripts:
FGFR1:ENST00000447712.7:c.91+13304del:p.(=)
Pathogenicity Data:
Best Score: 0.628283
REMM: 0.628
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 8-38428046-G-A [0/1] rs772054562
Variant score: 0.600
Transcripts:
FGFR1:ENST00000447712.7:c.496C>T:p.(His166Tyr)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_NFE: 0.0001%
gnomAD_E_SAS: 0.0012%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-38449656-C-A [0/1] rs150495210
Variant score: 0.452
Transcripts:
FGFR1:ENST00000447712.7:c.91+7700G>T:p.(=)
Pathogenicity Data:
Best Score: 0.677398
REMM: 0.677
Frequency Data:
UK10K: 0.8860%
gnomAD_G_AFR: 0.2003%
gnomAD_G_AMR: 0.8288%
gnomAD_G_NFE: 1.0659%
gnomAD_G_SAS: 1.2424%
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-38452200-G-GACAC [0/1] rs3051753
Variant score: 0.283
Transcripts:
FGFR1:ENST00000447712.7:c.91+5155_91+5156insGTGT:p.(=)
Pathogenicity Data:
Best Score: 0.328008
REMM: 0.328
Frequency Data:
gnomAD_G_AFR: 0.7057%
gnomAD_G_AMR: 0.4104%
gnomAD_G_EAS: 0.1067%
gnomAD_G_NFE: 0.2314%
gnomAD_G_SAS: 0.2440%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-38416212-A-C [0/1] rs113389616
Variant score: 0.051
Transcripts:
FGFR1:ENST00000447712.7:c.1664-152T>G:p.(=)
Pathogenicity Data:
Best Score: 0.0631976
REMM: 0.063
Frequency Data:
UK10K: 0.6215%
gnomAD_E_AFR: 0.8943%
gnomAD_E_AMR: 0.3130%
gnomAD_E_EAS: 0.0192%
gnomAD_E_NFE: 0.5168%
gnomAD_E_SAS: 0.1993%
gnomAD_G_AFR: 0.7247%
gnomAD_G_AMR: 0.3145%
gnomAD_G_EAS: 0.0774%
gnomAD_G_NFE: 0.5945%
gnomAD_G_SAS: 0.1245%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-38430048-C-T [0/1] rs986986368
Variant score: 0.008
Transcripts:
FGFR1:ENST00000447712.7:c.92-100G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00830198
REMM: 0.008
Frequency Data:
gnomAD_E_AMR: 0.0134%
gnomAD_E_NFE: 0.0045%
gnomAD_E_SAS: 0.0016%
gnomAD_G_NFE: 0.0029%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-38455794-G-A [0/1] rs147956471
Variant score: 0.004
Transcripts:
FGFR1:ENST00000447712.7:c.91+1562C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00670675
REMM: 0.007
Frequency Data:
UK10K: 0.1190%
gnomAD_G_AFR: 0.0385%
gnomAD_G_AMR: 0.2944%
gnomAD_G_NFE: 0.2897%
gnomAD_G_SAS: 1.2453%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-38429037-T-C [0/1]
Variant score: 0.002
Transcripts:
FGFR1:ENST00000447712.7:c.359-602A>G:p.(=)
Pathogenicity Data:
Best Score: 0.00183095
REMM: 0.002
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-38419362-A-G [0/1] rs17176002
Variant score: 0.001
Transcripts:
FGFR1:ENST00000447712.7:c.1284+171T>C:p.(=)
Pathogenicity Data:
Best Score: 0.00170397
REMM: 0.002
Frequency Data:
UK10K: 0.1190%
gnomAD_G_AFR: 0.0457%
gnomAD_G_AMR: 0.3922%
gnomAD_G_NFE: 0.3367%
gnomAD_G_SAS: 0.9324%

LAMB3

Exomiser Score: 0.393 (p=1.2E-1)

Phenotype Score: 0.502

Variant Score: 0.831

Phenotype matches:
Phenotypic similarity 0.293 to mouse mutant involving LAMB3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002100, abnormal tooth morphology
HP:0006625, Multifocal breast carcinoma - MP:0002100, abnormal tooth morphology
Proximity score 0.502 in interactome to ITGA3 and phenotypic similarity 0.603 to Epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome associated with ITGA3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Known diseases:
OMIM:104530 Amelogenesis imperfecta, type IA - autosomal dominant
OMIM:226650 Epidermolysis bullosa, junctional 1A, intermediate - autosomal recessive
OMIM:226700 Epidermolysis bullosa, junctional 1B, severe - autosomal recessive
ORPHA:79402 Intermediate generalized junctional epidermolysis bullosa - autosomal recessive
ORPHA:79404 Severe generalized junctional epidermolysis bullosa - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.393 (p=1.2E-1)

Phenotype Score: 0.502

Variant Score: 0.831

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-209626177-A-C [0/1] rs1197702711
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.831 CONTRIBUTING VARIANT
Transcripts:
LAMB3:ENST00000356082.9:c.1598-151T>G:p.(=)
Pathogenicity Data:
Best Score: 0.831678
REMM: 0.832
Frequency Data:
gnomAD_E_NFE: 0.0016%
gnomAD_E_SAS: 0.0020%
gnomAD_G_NFE: 0.0015%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.181 (p=2.1E-1)

Phenotype Score: 0.502

Variant Score: 0.714

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-209626177-A-C [0/1] rs1197702711
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.831 CONTRIBUTING VARIANT
Transcripts:
LAMB3:ENST00000356082.9:c.1598-151T>G:p.(=)
Pathogenicity Data:
Best Score: 0.831678
REMM: 0.832
Frequency Data:
gnomAD_E_NFE: 0.0016%
gnomAD_E_SAS: 0.0020%
gnomAD_G_NFE: 0.0015%
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-209624880-G-GAGGAAGGA [0/1] rs397962425
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.597 CONTRIBUTING VARIANT
Transcripts:
LAMB3:ENST00000356082.9:c.1976+767_1976+768insTCCTTCCT:p.(=)
Pathogenicity Data:
Best Score: 0.5973
REMM: 0.597
Frequency Data:
No frequency data
Other passed variants:
SYNONYMOUS_VARIANT SNV 1-209617434-G-A [0/1] rs768257008
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.100
Transcripts:
LAMB3:ENST00000356082.9:c.3204C>T:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 0.0030%
gnomAD_E_AMR: 0.0045%
gnomAD_E_EAS: 0.0050%
gnomAD_E_NFE: 0.0070%
gnomAD_E_SAS: 0.0128%
gnomAD_G_AFR: 0.0024%
gnomAD_G_NFE: 0.0015%

GNE

Exomiser Score: 0.384 (p=1.3E-1)

Phenotype Score: 0.502

Variant Score: 0.828

Phenotype matches:
Phenotypic similarity 0.573 to Sialuria associated with GNE.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0002557, Hypoplastic nipples
HP:0006625, Multifocal breast carcinoma - HP:0002557, Hypoplastic nipples
Proximity score 0.502 in interactome to CDKN2A and phenotypic similarity 0.998 to Familial pancreatic carcinoma associated with CDKN2A.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.502 in interactome to CDKN2A and phenotypic similarity 0.290 to mouse mutant of CDKN2A.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0003789, increased osteosarcoma incidence
HP:0006625, Multifocal breast carcinoma - MP:0003789, increased osteosarcoma incidence
Known diseases:
OMIM:269921 Sialuria - autosomal dominant
OMIM:605820 Nonaka myopathy - autosomal recessive
ORPHA:3166 Sialuria - autosomal dominant
ORPHA:602 GNE myopathy - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.384 (p=1.3E-1)

Phenotype Score: 0.502

Variant Score: 0.828

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.368 to ORPHA:602 GNE myopathy
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-36223076-A-G [0/1] rs182758289
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.839 CONTRIBUTING VARIANT
Transcripts:
GNE:ENST00000396594.8:c.1505-78T>C:p.(=)
GNE:ENST00000642385.2:c.1412-78T>C:p.(=)
Pathogenicity Data:
Best Score: 0.876438
REMM: 0.876
Frequency Data:
UK10K: 0.0397%
gnomAD_E_AFR: 0.0992%
gnomAD_E_AMR: 0.2765%
gnomAD_E_NFE: 0.0956%
gnomAD_E_SAS: 0.0447%
gnomAD_G_AFR: 0.0216%
gnomAD_G_AMR: 0.2482%
gnomAD_G_NFE: 0.0794%
gnomAD_G_SAS: 0.0414%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 9-36276642-GAA-G [0/1] rs753234844
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.816 CONTRIBUTING VARIANT
Transcripts:
GNE:ENST00000396594.8:c.51+250_51+251del:p.(=)
Pathogenicity Data:
Best Score: 0.848817
REMM: 0.849
Frequency Data:
UK10K: 0.0397%
gnomAD_G_AFR: 0.0216%
gnomAD_G_AMR: 0.2484%
gnomAD_G_NFE: 0.0808%
gnomAD_G_SAS: 0.0414%
Other passed variants:
THREE_PRIME_UTR_EXON_VARIANT INS 9-36216327-A-ATGTGTGTGTGTGTGTGTGTGTGTGTGTGTG [0/1] rs10527967
Variant score: 0.736
Transcripts:
GNE:ENST00000396594.8:c.*1037_*1038insCACACACACACACACACACACACACACACA:p.(=)
GNE:ENST00000642385.2:c.*1037_*1038insCACACACACACACACACACACACACACACA:p.(=)
Pathogenicity Data:
Best Score: 0.89249
REMM: 0.892
Frequency Data:
gnomAD_G_AFR: 0.6415%
gnomAD_G_AMR: 0.4776%
gnomAD_G_EAS: 0.0819%
gnomAD_G_NFE: 0.8310%
gnomAD_G_SAS: 0.6392%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 9-36272620-CAAA-C [1/1]
Variant score: 0.500
Transcripts:
GNE:ENST00000396594.8:c.51+4271_51+4273del:p.(=)
Pathogenicity Data:
Best Score: 0.50038
REMM: 0.500
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-36246681-T-G [1/1] rs10758351
Variant score: 0.457
Transcripts:
GNE:ENST00000396594.8:c.258-199A>C:p.(=)
GNE:ENST00000642385.2:c.165-199A>C:p.(=)
Pathogenicity Data:
Best Score: 0.456597
REMM: 0.457
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 9-36256239-CTTTTTTTT-C [1/1] rs34215482
Variant score: 0.349
Transcripts:
GNE:ENST00000396594.8:c.52-6850_52-6843del:p.(=)
GNE:ENST00000642385.2:c.-43+2074_-43+2081del:p.(=)
Pathogenicity Data:
Best Score: 0.34944
REMM: 0.349
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-36261386-G-A [0/1] rs544671286
Variant score: 0.217
Transcripts:
GNE:ENST00000396594.8:c.52-11989C>T:p.(=)
Pathogenicity Data:
Best Score: 0.226101
REMM: 0.226
Frequency Data:
UK10K: 0.0529%
gnomAD_G_AFR: 0.0340%
gnomAD_G_AMR: 0.2642%
gnomAD_G_NFE: 0.1048%
gnomAD_G_SAS: 0.0419%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-36248613-C-T [0/1] rs141059109
Variant score: 0.006
Transcripts:
GNE:ENST00000396594.8:c.257+579G>A:p.(=)
GNE:ENST00000642385.2:c.164+579G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00608889
REMM: 0.006
Frequency Data:
UK10K: 0.1587%
gnomAD_G_AFR: 0.0650%
gnomAD_G_AMR: 0.4851%
gnomAD_G_NFE: 0.1941%
gnomAD_G_SAS: 0.0416%

XIAP

Exomiser Score: 0.379 (p=1.3E-1)

Phenotype Score: 0.504

Variant Score: 0.823

Phenotype matches:
Proximity score 0.504 in interactome to CASP10 and phenotypic similarity 0.876 to Autoimmune lymphoproliferative syndrome associated with CASP10.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010619, Fibroadenoma of the breast
HP:0006625, Multifocal breast carcinoma - HP:0010619, Fibroadenoma of the breast
Known diseases:
OMIM:300635 Lymphoproliferative syndrome, X-linked, 2 - X-linked recessive
Gene scores under compatible inheritance modes:

X_RECESSIVE

Exomiser Score: 0.379 (p=1.3E-1)

Phenotype Score: 0.504

Variant Score: 0.823

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL X-123889997-ATTTTTTTTT-A [1/1] rs771503633
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.823 CONTRIBUTING VARIANT
Transcripts:
XIAP:ENST00000371199.8:c.978-1240_978-1232del:p.(=)
Pathogenicity Data:
Best Score: 0.823288
REMM: 0.823
Frequency Data:
No frequency data

X_DOMINANT

Exomiser Score: 0.043 (p=3.4E-1)

Phenotype Score: 0.252

Variant Score: 0.823

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL X-123889997-ATTTTTTTTT-A [1/1] rs771503633
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.823 CONTRIBUTING VARIANT
Transcripts:
XIAP:ENST00000371199.8:c.978-1240_978-1232del:p.(=)
Pathogenicity Data:
Best Score: 0.823288
REMM: 0.823
Frequency Data:
No frequency data
Other passed variants:
FIVE_PRIME_UTR_INTRON_VARIANT INS X-123869362-C-CAAAAAAAAAAAAAAAAAAAAAAA [0/1] rs57436822
Variant score: 0.604
Transcripts:
XIAP:ENST00000371199.8:c.-33+9069_-33+9070insAAAAAAAAAAAAAAAAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.626373
REMM: 0.626
Frequency Data:
gnomAD_G_AFR: 0.0900%
gnomAD_G_AMR: 0.1091%
gnomAD_G_EAS: 0.0922%
gnomAD_G_NFE: 0.2353%
FIVE_PRIME_UTR_INTRON_VARIANT INS X-123869362-C-CAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA [0/1] rs57436822
Variant score: 0.594
Transcripts:
XIAP:ENST00000371199.8:c.-33+9069_-33+9070insAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.626373
REMM: 0.626
Frequency Data:
gnomAD_G_AFR: 0.0750%
gnomAD_G_AMR: 0.3275%
gnomAD_G_NFE: 0.0673%
INTERGENIC_VARIANT DEL X-123843252-CT-C [0/1] rs754021116
Variant score: 0.374
Transcripts:
XIAP:ENST00000371199.8::
Pathogenicity Data:
Best Score: 0.374089
REMM: 0.374
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT DEL X-123874869-ATT-A [1/1] rs773693860
Variant score: 0.354
Transcripts:
XIAP:ENST00000371199.8:c.-32-10761_-32-10760del:p.(=)
Pathogenicity Data:
Best Score: 0.354072
REMM: 0.354
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT INS X-123864455-G-GT [1/1] rs1162636021
Variant score: 0.278
Transcripts:
XIAP:ENST00000371199.8:c.-33+4162_-33+4163insT:p.(=)
Pathogenicity Data:
Best Score: 0.278353
REMM: 0.278
Frequency Data:
No frequency data

ITPR3

Exomiser Score: 0.376 (p=1.3E-1)

Phenotype Score: 0.504

Variant Score: 0.821

Phenotype matches:
Phenotypic similarity 0.326 to zebrafish mutant involving ITPR3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0001460, notochord deformed, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0001460, notochord deformed, abnormal
Proximity score 0.504 in interactome to RASGRP1 and phenotypic similarity 0.876 to Autoimmune lymphoproliferative syndrome associated with RASGRP1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010619, Fibroadenoma of the breast
HP:0006625, Multifocal breast carcinoma - HP:0010619, Fibroadenoma of the breast
Proximity score 0.504 in interactome to RASGRP1 and phenotypic similarity 0.207 to mouse mutant of RASGRP1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002145, abnormal T cell differentiation
HP:0006625, Multifocal breast carcinoma - MP:0002145, abnormal T cell differentiation
Known diseases:
OMIM:222100 Diabetes, type 1, susceptibility to (susceptibility)
OMIM:620111 Charcot-Marie-Tooth disease, demyelinating, type 1J - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.376 (p=1.3E-1)

Phenotype Score: 0.504

Variant Score: 0.821

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-33673222-G-A [0/1] rs776198186
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.821 CONTRIBUTING VARIANT
Transcripts:
ITPR3:ENST00000605930.3:c.2929-369G>A:p.(=)
Pathogenicity Data:
Best Score: 0.824208
REMM: 0.824
Frequency Data:
UK10K: 0.0264%
gnomAD_G_AFR: 0.0024%
gnomAD_G_NFE: 0.0118%
gnomAD_G_SAS: 0.0207%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.179 (p=2.1E-1)

Phenotype Score: 0.504

Variant Score: 0.711

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-33673222-G-A [0/1] rs776198186
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.821 CONTRIBUTING VARIANT
Transcripts:
ITPR3:ENST00000605930.3:c.2929-369G>A:p.(=)
Pathogenicity Data:
Best Score: 0.824208
REMM: 0.824
Frequency Data:
UK10K: 0.0264%
gnomAD_G_AFR: 0.0024%
gnomAD_G_NFE: 0.0118%
gnomAD_G_SAS: 0.0207%
MISSENSE_VARIANT SNV 6-33657939-C-T [0/1] rs138371134
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.600 CONTRIBUTING VARIANT
Transcripts:
ITPR3:ENST00000605930.3:c.290C>T:p.(Ala97Val)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_NFE: 0.0016%
gnomAD_E_SAS: 0.0012%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-33661992-G-GAAAAAAAAAAAAAAAAA [0/1]
Variant score: 0.267
Transcripts:
ITPR3:ENST00000605930.3:c.712-536_712-535insAAAAAAAAAAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.266704
REMM: 0.267
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-33636123-CAA-C [0/1]
Variant score: 0.167
Transcripts:
ITPR3:ENST00000605930.3:c.90-4360_90-4359del:p.(=)
Pathogenicity Data:
Best Score: 0.166683
REMM: 0.167
Frequency Data:
No frequency data
SYNONYMOUS_VARIANT SNV 6-33679962-C-T [0/1] rs142408977
Variant score: 0.099
Transcripts:
ITPR3:ENST00000605930.3:c.4053C>T:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 0.0060%
gnomAD_E_NFE: 0.0092%
gnomAD_E_SAS: 0.0580%
gnomAD_G_AFR: 0.0024%
gnomAD_G_NFE: 0.0044%
gnomAD_G_SAS: 0.0414%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-33623326-G-T [1/1]
Variant score: 0.017
Transcripts:
ITPR3:ENST00000605930.3:c.89+1635G>T:p.(=)
Pathogenicity Data:
Best Score: 0.0174901
REMM: 0.017
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 6-33606131-A-G [1|1] rs2988057
Variant score: 0.009
Transcripts:
ITPR3:ENST00000605930.3::
Pathogenicity Data:
Best Score: 0.00945159
REMM: 0.009
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 6-33606236-T-C [0|1] rs184113
Variant score: 0.009
Transcripts:
ITPR3:ENST00000605930.3::
Pathogenicity Data:
Best Score: 0.00937778
REMM: 0.009
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 6-33606247-A-G [0|1] rs141537370
Variant score: 0.009
Transcripts:
ITPR3:ENST00000605930.3::
Pathogenicity Data:
Best Score: 0.0087
REMM: 0.009
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 6-33606234-C-T [0/1] rs57228192
Variant score: 0.008
Transcripts:
ITPR3:ENST00000605930.3::
Pathogenicity Data:
Best Score: 0.00826667
REMM: 0.008
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 6-33606265-G-T [0|1] rs947978759
Variant score: 0.005
Transcripts:
ITPR3:ENST00000605930.3::
Pathogenicity Data:
Best Score: 0.00547778
REMM: 0.005
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-33693335-G-A [0|1] rs116657129
Variant score: 0.003
Transcripts:
ITPR3:ENST00000605930.3:c.7625-210G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00322063
REMM: 0.003
Frequency Data:
UK10K: 0.5422%
gnomAD_G_AFR: 0.1516%
gnomAD_G_AMR: 0.5558%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.7454%
gnomAD_G_SAS: 0.4764%

BAIAP2

Exomiser Score: 0.332 (p=1.4E-1)

Phenotype Score: 0.504

Variant Score: 0.800

Phenotype matches:
Phenotypic similarity 0.329 to mouse mutant involving BAIAP2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0005508, abnormal skeleton morphology
HP:0006625, Multifocal breast carcinoma - MP:0005508, abnormal skeleton morphology
Proximity score 0.504 in interactome to WASF1 and phenotypic similarity 0.635 to Neurodevelopmental disorder with absent language and variable seizures associated with WASF1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.332 (p=1.4E-1)

Phenotype Score: 0.504

Variant Score: 0.800

No phenotype matches to diseases with this MOI.
Variants contributing to score:
SPLICE_REGION_VARIANT DEL 17-81057973-ACC-A [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.800 CONTRIBUTING VARIANT
Transcripts:
BAIAP2:ENST00000428708.7:c.217+7_217+8del:p.?
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.242 (p=1.8E-1)

Phenotype Score: 0.504

Variant Score: 0.752

No phenotype matches to diseases with this MOI.
Variants contributing to score:
SPLICE_REGION_VARIANT DEL 17-81057973-ACC-A [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.800 CONTRIBUTING VARIANT
Transcripts:
BAIAP2:ENST00000428708.7:c.217+7_217+8del:p.?
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-81065309-C-T [0/1] rs538872387
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.704 CONTRIBUTING VARIANT
Transcripts:
BAIAP2:ENST00000428708.7:c.217+7342C>T:p.(=)
Pathogenicity Data:
Best Score: 0.779274
REMM: 0.779
Frequency Data:
UK10K: 0.2380%
gnomAD_G_AFR: 0.0192%
gnomAD_G_AMR: 0.0196%
gnomAD_G_NFE: 0.1735%
gnomAD_G_SAS: 0.5394%
Other passed variants:
INTERGENIC_VARIANT SNV 17-81022885-G-A [0/1] rs1360002054
Variant score: 0.437
Transcripts:
BAIAP2:ENST00000428708.7::
Pathogenicity Data:
Best Score: 0.437425
REMM: 0.437
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 17-81022891-G-A [1/1] rs1366948165
Variant score: 0.294
Transcripts:
BAIAP2:ENST00000428708.7::
Pathogenicity Data:
Best Score: 0.295877
REMM: 0.296
Frequency Data:
gnomAD_G_NFE: 0.0363%
INTERGENIC_VARIANT SNV 17-81022761-T-C [1/1]
Variant score: 0.270
Transcripts:
BAIAP2:ENST00000428708.7::
Pathogenicity Data:
Best Score: 0.270194
REMM: 0.270
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 17-81022902-A-G [1/1]
Variant score: 0.258
Transcripts:
BAIAP2:ENST00000428708.7::
Pathogenicity Data:
Best Score: 0.257841
REMM: 0.258
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 17-81022881-T-C [0/1]
Variant score: 0.256
Transcripts:
BAIAP2:ENST00000428708.7::
Pathogenicity Data:
Best Score: 0.255511
REMM: 0.256
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-81108631-C-CACCCCTGTCAGAGCCGGGGATGTCCCTTA [0/1]
Variant score: 0.100
Transcripts:
BAIAP2:ENST00000428708.7:c.1535+122_1535+123insACCCCTGTCAGAGCCGGGGATGTCCCTTA:p.(=)
Pathogenicity Data:
Best Score: 0.0999655
REMM: 0.100
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-81057990-G-C [0/1]
Variant score: 0.034
Transcripts:
BAIAP2:ENST00000428708.7:c.217+23G>C:p.(=)
Pathogenicity Data:
Best Score: 0.0337766
REMM: 0.034
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 17-81048356-CAA-C [0/1]
Variant score: 0.028
Transcripts:
BAIAP2:ENST00000428708.7:c.55-5311_55-5310del:p.(=)
Pathogenicity Data:
Best Score: 0.0276452
REMM: 0.028
Frequency Data:
No frequency data

RAF1

Exomiser Score: 0.332 (p=1.4E-1)

Phenotype Score: 0.558

Variant Score: 0.739

Phenotype matches:
Phenotypic similarity 0.558 to Noonan syndrome associated with RAF1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0006610, Wide intermamillary distance
HP:0006625, Multifocal breast carcinoma - HP:0006610, Wide intermamillary distance
Phenotypic similarity 0.362 to mouse mutant involving RAF1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0010031, abnormal cranium size
HP:0006625, Multifocal breast carcinoma - MP:0010031, abnormal cranium size
Proximity score 0.511 in interactome to SPRY4 and phenotypic similarity 0.620 to Kallmann syndrome associated with SPRY4.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003187, Breast hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0003187, Breast hypoplasia
Proximity score 0.511 in interactome to SPRY4 and phenotypic similarity 0.294 to mouse mutant of SPRY4.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000458, abnormal mandible morphology
HP:0006625, Multifocal breast carcinoma - MP:0000458, abnormal mandible morphology
Known diseases:
OMIM:611553 Noonan syndrome 5 - autosomal dominant
OMIM:611554 LEOPARD syndrome 2 - autosomal dominant
OMIM:615916 Cardiomyopathy, dilated, 1NN - autosomal dominant
ORPHA:154 Familial isolated dilated cardiomyopathy - autosomal dominant
ORPHA:500 Noonan syndrome with multiple lentigines - autosomal dominant
ORPHA:626 Large congenital melanocytic nevus (unconfirmed)
ORPHA:648 Noonan syndrome - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.332 (p=1.4E-1)

Phenotype Score: 0.558

Variant Score: 0.739

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.558 to ORPHA:648 Noonan syndrome
Phenotypic similarity 0.484 to OMIM:611554 LEOPARD syndrome 2
Phenotypic similarity 0.484 to OMIM:611553 Noonan syndrome 5
Phenotypic similarity 0.448 to ORPHA:500 Noonan syndrome with multiple lentigines
Variants contributing to score:
FIVE_PRIME_UTR_INTRON_VARIANT INS 3-12659427-C-CAAAAAAAAAAAAAAAAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.739 CONTRIBUTING VARIANT
Transcripts:
RAF1:ENST00000251849.9:c.-27+4385_-27+4386insTTTTTTTTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.738505
REMM: 0.739
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.021 (p=4.0E-1)

Phenotype Score: 0.255

Variant Score: 0.739

No phenotype matches to diseases with this MOI.
Variants contributing to score:
FIVE_PRIME_UTR_INTRON_VARIANT INS 3-12659427-C-CAAAAAAAAAAAAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.739 CONTRIBUTING VARIANT
Transcripts:
RAF1:ENST00000251849.9:c.-27+4385_-27+4386insTTTTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.738505
REMM: 0.739
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT INS 3-12659427-C-CAAAAAAAAAAAAAAAAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.739 CONTRIBUTING VARIANT
Transcripts:
RAF1:ENST00000251849.9:c.-27+4385_-27+4386insTTTTTTTTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.738505
REMM: 0.739
Frequency Data:
No frequency data
Other passed variants:
FIVE_PRIME_UTR_INTRON_VARIANT DEL 3-12662338-TAAAA-T [0/1]
Variant score: 0.726
Transcripts:
RAF1:ENST00000251849.9:c.-27+1471_-27+1474del:p.(=)
Pathogenicity Data:
Best Score: 0.725896
REMM: 0.726
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT DEL 3-12662338-TAAAAAAAAAA-T [0/1]
Variant score: 0.726
Transcripts:
RAF1:ENST00000251849.9:c.-27+1465_-27+1474del:p.(=)
Pathogenicity Data:
Best Score: 0.725896
REMM: 0.726
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 3-12598725-CAAAA-C [0/1]
Variant score: 0.417
Transcripts:
RAF1:ENST00000251849.9:c.1108+962_1108+965del:p.(=)
Pathogenicity Data:
Best Score: 0.417208
REMM: 0.417
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 3-12607949-C-CAAAAA [0/1] rs58308841
Variant score: 0.095
Transcripts:
RAF1:ENST00000251849.9:c.581+816_581+817insTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.419986
REMM: 0.420
Frequency Data:
gnomAD_G_AFR: 0.9050%
gnomAD_G_AMR: 1.6805%
gnomAD_G_NFE: 1.9038%
gnomAD_G_SAS: 0.6849%
SYNONYMOUS_VARIANT SNV 3-12584520-G-A [0/1] rs3730297
ClinVar: BENIGN (REVIEWED_BY_EXPERT_PANEL)
Variant score: 0.068
Transcripts:
RAF1:ENST00000251849.9:c.1941C>T:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 1.2166%
gnomAD_E_AFR: 0.1016%
gnomAD_E_AMR: 0.4450%
gnomAD_E_EAS: 0.0025%
gnomAD_E_NFE: 1.1495%
gnomAD_E_SAS: 0.1797%
gnomAD_G_AFR: 0.1780%
gnomAD_G_AMR: 1.0137%
gnomAD_G_NFE: 1.0318%
gnomAD_G_SAS: 0.1863%

PDGFRB

Exomiser Score: 0.331 (p=1.4E-1)

Phenotype Score: 0.504

Variant Score: 0.799

Phenotype matches:
Phenotypic similarity 0.504 to Infantile myofibromatosis associated with PDGFRB.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000765, Abnormal thorax morphology
HP:0006625, Multifocal breast carcinoma - HP:0000765, Abnormal thorax morphology
Phenotypic similarity 0.321 to mouse mutant involving PDGFRB.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002639, micrognathia
HP:0006625, Multifocal breast carcinoma - MP:0002639, micrognathia
Proximity score 0.503 in interactome to FGF17 and phenotypic similarity 0.620 to Kallmann syndrome associated with FGF17.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003187, Breast hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0003187, Breast hypoplasia
Known diseases:
OMIM:131440 Myeloproliferative disorder with eosinophilia (CNV)
OMIM:228550 Myofibromatosis, infantile, 1 - autosomal dominant
OMIM:601812 Premature aging syndrome, Penttinen type - autosomal dominant
OMIM:615007 Basal ganglia calcification, idiopathic, 4 - autosomal dominant
OMIM:616592 Kosaki overgrowth syndrome - autosomal dominant
ORPHA:1980 Bilateral striopallidodentate calcinosis - autosomal dominant
ORPHA:2591 Infantile myofibromatosis - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.331 (p=1.4E-1)

Phenotype Score: 0.504

Variant Score: 0.799

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.504 to ORPHA:2591 Infantile myofibromatosis
Phenotypic similarity 0.432 to OMIM:601812 Premature aging syndrome, Penttinen type
Variants contributing to score:
SPLICE_REGION_VARIANT SNV 5-150124244-C-T [0/1] rs778954389
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.799 CONTRIBUTING VARIANT
Transcripts:
PDGFRB:ENST00000261799.9:c.2023+6G>A:p.?
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_NFE: 0.0029%
gnomAD_E_SAS: 0.0012%
gnomAD_G_NFE: 0.0059%

ESRRB

Exomiser Score: 0.331 (p=1.4E-1)

Phenotype Score: 0.502

Variant Score: 0.802

Phenotype matches:
Proximity score 0.502 in interactome to NR5A1 and phenotypic similarity 0.676 to 46,XX gonadal dysgenesis associated with NR5A1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
HP:0006625, Multifocal breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
Known diseases:
OMIM:608565 Deafness, autosomal recessive 35 - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.331 (p=1.4E-1)

Phenotype Score: 0.502

Variant Score: 0.802

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76379435-C-A [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.975 CONTRIBUTING VARIANT
Transcripts:
ESRRB:ENST00000644823.1:c.50+2984C>A:p.(=)
Pathogenicity Data:
Best Score: 0.97491
REMM: 0.975
Frequency Data:
No frequency data
THREE_PRIME_UTR_EXON_VARIANT SNV 14-76500004-C-T [0/1] rs201448899
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:6, LB:2)
Variant score: 0.629 CONTRIBUTING VARIANT
Transcripts:
ESRRB:ENST00000644823.1:c.*1546C>T:p.(=)
Pathogenicity Data:
Best Score: 0.647273
REMM: 0.647
Frequency Data:
UK10K: 0.0397%
gnomAD_E_AFR: 0.0122%
gnomAD_E_AMR: 0.1356%
gnomAD_E_NFE: 0.1062%
gnomAD_E_SAS: 0.0284%
gnomAD_G_AFR: 0.0241%
gnomAD_G_AMR: 0.1895%
gnomAD_G_NFE: 0.1205%
gnomAD_G_SAS: 0.0415%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.151 (p=2.3E-1)

Phenotype Score: 0.251

Variant Score: 0.975

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76379435-C-A [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.975 CONTRIBUTING VARIANT
Transcripts:
ESRRB:ENST00000644823.1:c.50+2984C>A:p.(=)
Pathogenicity Data:
Best Score: 0.97491
REMM: 0.975
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76489856-G-C [0/1] rs180947155
Variant score: 0.540
Transcripts:
ESRRB:ENST00000644823.1:c.851-1591G>C:p.(=)
Pathogenicity Data:
Best Score: 0.688073
REMM: 0.688
Frequency Data:
UK10K: 0.9521%
gnomAD_G_AFR: 0.1710%
gnomAD_G_AMR: 0.8626%
gnomAD_G_EAS: 0.3480%
gnomAD_G_NFE: 0.8907%
gnomAD_G_SAS: 0.3730%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76430316-G-A [0/1] rs146992911
Variant score: 0.456
Transcripts:
ESRRB:ENST00000644823.1:c.51-9025G>A:p.(=)
Pathogenicity Data:
Best Score: 0.883985
REMM: 0.884
Frequency Data:
UK10K: 1.5208%
gnomAD_G_AFR: 0.2913%
gnomAD_G_AMR: 1.4654%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.5095%
gnomAD_G_SAS: 1.1628%
CODING_TRANSCRIPT_INTRON_VARIANT INS 14-76419869-A-AG [0/1] rs202135868
Variant score: 0.443
Transcripts:
ESRRB:ENST00000644823.1:c.51-19472_51-19471insG:p.(=)
Pathogenicity Data:
Best Score: 0.858179
REMM: 0.858
Frequency Data:
UK10K: 1.5208%
gnomAD_G_AFR: 0.2890%
gnomAD_G_AMR: 1.4581%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 1.5146%
gnomAD_G_SAS: 1.1662%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76456831-G-C [0/1] rs149590620
Variant score: 0.443
Transcripts:
ESRRB:ENST00000644823.1:c.461-5714G>C:p.(=)
Pathogenicity Data:
Best Score: 0.815222
REMM: 0.815
Frequency Data:
UK10K: 1.4282%
gnomAD_G_AFR: 0.2935%
gnomAD_G_AMR: 1.4646%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.4760%
gnomAD_G_SAS: 0.5595%
CODING_TRANSCRIPT_INTRON_VARIANT INS 14-76447243-C-CTCCT [0/1] rs11272399
Variant score: 0.442
Transcripts:
ESRRB:ENST00000644823.1:c.460+7493_460+7494insTCCT:p.(=)
Pathogenicity Data:
Best Score: 0.44157
REMM: 0.442
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76414054-G-C [0/1]
Variant score: 0.433
Transcripts:
ESRRB:ENST00000644823.1:c.51-25287G>C:p.(=)
Pathogenicity Data:
Best Score: 0.432786
REMM: 0.433
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76412499-G-A [0/1] rs147949300
Variant score: 0.428
Transcripts:
ESRRB:ENST00000644823.1:c.51-26842G>A:p.(=)
Pathogenicity Data:
Best Score: 0.863378
REMM: 0.863
Frequency Data:
UK10K: 1.5472%
gnomAD_G_AFR: 0.2963%
gnomAD_G_AMR: 1.4664%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.5532%
gnomAD_G_SAS: 1.1628%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76453277-A-T [0/1] rs118052959
Variant score: 0.422
Transcripts:
ESRRB:ENST00000644823.1:c.461-9268A>T:p.(=)
Pathogenicity Data:
Best Score: 0.77773
REMM: 0.778
Frequency Data:
UK10K: 1.4282%
gnomAD_G_AFR: 0.2934%
gnomAD_G_AMR: 1.4698%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.4771%
gnomAD_G_SAS: 0.5592%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 14-76468390-GCC-G [0|1] rs377124404
Variant score: 0.417
Transcripts:
ESRRB:ENST00000644823.1:c.577+5730_577+5731del:p.(=)
Pathogenicity Data:
Best Score: 0.772858
REMM: 0.773
Frequency Data:
UK10K: 1.4811%
gnomAD_G_AFR: 0.9852%
gnomAD_G_AMR: 1.1955%
gnomAD_G_EAS: 0.1815%
gnomAD_G_NFE: 1.4322%
gnomAD_G_SAS: 0.3046%
CODING_TRANSCRIPT_INTRON_VARIANT INS 14-76450581-T-TGGCACAGTGCTTCCTCCCG [0/1] rs202028265
Variant score: 0.402
Transcripts:
ESRRB:ENST00000644823.1:c.460+10831_460+10832insGGCACAGTGCTTCCTCCCG:p.(=)
Pathogenicity Data:
Best Score: 0.776869
REMM: 0.777
Frequency Data:
UK10K: 0.8728%
gnomAD_G_AFR: 0.2888%
gnomAD_G_AMR: 1.4332%
gnomAD_G_EAS: 0.0387%
gnomAD_G_NFE: 1.5177%
gnomAD_G_SAS: 1.2251%
CODING_TRANSCRIPT_INTRON_VARIANT INS 14-76434152-A-AT [0/1] rs201171184
Variant score: 0.372
Transcripts:
ESRRB:ENST00000644823.1:c.51-5189_51-5188insT:p.(=)
Pathogenicity Data:
Best Score: 0.7128
REMM: 0.713
Frequency Data:
UK10K: 1.5075%
gnomAD_G_AFR: 0.2918%
gnomAD_G_AMR: 1.4669%
gnomAD_G_EAS: 0.0195%
gnomAD_G_NFE: 1.5106%
gnomAD_G_SAS: 1.2276%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76459185-G-T [0/1] rs118075789
Variant score: 0.365
Transcripts:
ESRRB:ENST00000644823.1:c.461-3360G>T:p.(=)
Pathogenicity Data:
Best Score: 0.699835
REMM: 0.700
Frequency Data:
UK10K: 1.4811%
gnomAD_G_AFR: 0.2960%
gnomAD_G_AMR: 1.4775%
gnomAD_G_EAS: 0.0387%
gnomAD_G_NFE: 1.5114%
gnomAD_G_SAS: 1.2635%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76424801-A-G [0/1] rs144886528
Variant score: 0.360
Transcripts:
ESRRB:ENST00000644823.1:c.51-14540A>G:p.(=)
Pathogenicity Data:
Best Score: 0.521429
REMM: 0.521
Frequency Data:
UK10K: 1.1902%
gnomAD_G_AFR: 0.2503%
gnomAD_G_AMR: 1.1636%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.1895%
gnomAD_G_SAS: 0.4155%
CODING_TRANSCRIPT_INTRON_VARIANT INS 14-76485404-A-AT [0/1] rs199913144
Variant score: 0.360
Transcripts:
ESRRB:ENST00000644823.1:c.850+2645_850+2646insT:p.(=)
Pathogenicity Data:
Best Score: 0.635535
REMM: 0.636
Frequency Data:
gnomAD_G_AFR: 0.2863%
gnomAD_G_AMR: 1.1739%
gnomAD_G_EAS: 1.4370%
gnomAD_G_NFE: 1.3209%
gnomAD_G_SAS: 0.5742%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76419937-G-A [0/1] rs116938807
Variant score: 0.352
Transcripts:
ESRRB:ENST00000644823.1:c.51-19404G>A:p.(=)
Pathogenicity Data:
Best Score: 0.69363
REMM: 0.694
Frequency Data:
UK10K: 1.5340%
gnomAD_G_AFR: 0.2915%
gnomAD_G_AMR: 1.4725%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.5163%
gnomAD_G_SAS: 1.1401%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76425075-C-G [0/1] rs117204696
Variant score: 0.348
Transcripts:
ESRRB:ENST00000644823.1:c.51-14266C>G:p.(=)
Pathogenicity Data:
Best Score: 0.684427
REMM: 0.684
Frequency Data:
UK10K: 1.5340%
gnomAD_G_AFR: 0.2938%
gnomAD_G_AMR: 1.4731%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 1.5073%
gnomAD_G_SAS: 1.1657%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 14-76414162-TC-T [0/1]
Variant score: 0.344
Transcripts:
ESRRB:ENST00000644823.1:c.51-25178del:p.(=)
Pathogenicity Data:
Best Score: 0.344229
REMM: 0.344
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76429289-G-A [0/1] rs117819846
Variant score: 0.322
Transcripts:
ESRRB:ENST00000644823.1:c.51-10052G>A:p.(=)
Pathogenicity Data:
Best Score: 0.633095
REMM: 0.633
Frequency Data:
UK10K: 1.5340%
gnomAD_G_AFR: 0.2936%
gnomAD_G_AMR: 1.4721%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.5086%
gnomAD_G_SAS: 1.1628%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76436144-G-T [0/1] rs117704530
Variant score: 0.318
Transcripts:
ESRRB:ENST00000644823.1:c.51-3197G>T:p.(=)
Pathogenicity Data:
Best Score: 0.587347
REMM: 0.587
Frequency Data:
UK10K: 1.4150%
gnomAD_G_AFR: 0.2861%
gnomAD_G_AMR: 1.4506%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.4800%
gnomAD_G_SAS: 0.5390%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 14-76417944-CTT-C [0/1] rs869242837
Variant score: 0.313
Transcripts:
ESRRB:ENST00000644823.1:c.51-21396_51-21395del:p.(=)
Pathogenicity Data:
Best Score: 0.712492
REMM: 0.712
Frequency Data:
gnomAD_G_AFR: 0.6687%
gnomAD_G_AMR: 1.4541%
gnomAD_G_EAS: 0.0363%
gnomAD_G_NFE: 1.6372%
gnomAD_G_SAS: 1.4079%
CODING_TRANSCRIPT_INTRON_VARIANT INS 14-76422206-C-CTTTT [0/1] rs552738537
Variant score: 0.292
Transcripts:
ESRRB:ENST00000644823.1:c.51-17135_51-17134insTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.45651
REMM: 0.457
Frequency Data:
gnomAD_G_AFR: 0.3481%
gnomAD_G_AMR: 0.9596%
gnomAD_G_EAS: 0.0299%
gnomAD_G_NFE: 1.2966%
gnomAD_G_SAS: 0.5810%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76466623-A-T [0/1] rs118023258
Variant score: 0.290
Transcripts:
ESRRB:ENST00000644823.1:c.577+3962A>T:p.(=)
Pathogenicity Data:
Best Score: 0.522219
REMM: 0.522
Frequency Data:
UK10K: 1.4546%
gnomAD_G_AFR: 0.2888%
gnomAD_G_AMR: 1.3597%
gnomAD_G_EAS: 0.1935%
gnomAD_G_NFE: 1.4364%
gnomAD_G_SAS: 0.6424%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 14-76431331-CTCT-C [0/1] rs199667611
Variant score: 0.280
Transcripts:
ESRRB:ENST00000644823.1:c.51-8009_51-8007del:p.(=)
Pathogenicity Data:
Best Score: 0.552069
REMM: 0.552
Frequency Data:
UK10K: 1.5340%
gnomAD_G_AFR: 0.2887%
gnomAD_G_AMR: 1.4725%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.5099%
gnomAD_G_SAS: 1.1821%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76450732-A-T [0/1] rs137882447
Variant score: 0.276
Transcripts:
ESRRB:ENST00000644823.1:c.460+10982A>T:p.(=)
Pathogenicity Data:
Best Score: 0.513211
REMM: 0.513
Frequency Data:
UK10K: 1.4414%
gnomAD_G_AFR: 0.2938%
gnomAD_G_AMR: 1.4517%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 1.4840%
gnomAD_G_SAS: 0.5611%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76465453-G-A [0/1] rs117571690
Variant score: 0.267
Transcripts:
ESRRB:ENST00000644823.1:c.577+2792G>A:p.(=)
Pathogenicity Data:
Best Score: 0.502127
REMM: 0.502
Frequency Data:
UK10K: 1.4943%
gnomAD_G_AFR: 0.2936%
gnomAD_G_AMR: 1.3793%
gnomAD_G_EAS: 0.1349%
gnomAD_G_NFE: 1.4704%
gnomAD_G_SAS: 1.3071%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76445143-A-G [0/1] rs146963701
Variant score: 0.264
Transcripts:
ESRRB:ENST00000644823.1:c.460+5393A>G:p.(=)
Pathogenicity Data:
Best Score: 0.531312
REMM: 0.531
Frequency Data:
gnomAD_G_AFR: 0.2966%
gnomAD_G_AMR: 1.4450%
gnomAD_G_NFE: 1.5504%
gnomAD_G_SAS: 1.3527%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76488390-C-A [0/1] rs116968367
Variant score: 0.247
Transcripts:
ESRRB:ENST00000644823.1:c.851-3057C>A:p.(=)
Pathogenicity Data:
Best Score: 0.482887
REMM: 0.483
Frequency Data:
UK10K: 1.3753%
gnomAD_G_AFR: 0.2647%
gnomAD_G_AMR: 1.1707%
gnomAD_G_EAS: 1.5269%
gnomAD_G_NFE: 1.2937%
gnomAD_G_SAS: 0.4977%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76463777-A-G [0/1] rs150928538
Variant score: 0.246
Transcripts:
ESRRB:ENST00000644823.1:c.577+1116A>G:p.(=)
Pathogenicity Data:
Best Score: 0.461312
REMM: 0.461
Frequency Data:
UK10K: 1.4943%
gnomAD_G_AFR: 0.2941%
gnomAD_G_AMR: 1.3885%
gnomAD_G_EAS: 0.1545%
gnomAD_G_NFE: 1.4765%
gnomAD_G_SAS: 1.3076%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76415275-T-C [0/1] rs118119128
Variant score: 0.216
Transcripts:
ESRRB:ENST00000644823.1:c.51-24066T>C:p.(=)
Pathogenicity Data:
Best Score: 0.313565
REMM: 0.314
Frequency Data:
UK10K: 1.1637%
gnomAD_G_AFR: 0.2502%
gnomAD_G_AMR: 1.1629%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.1936%
gnomAD_G_SAS: 0.3937%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 14-76411449-CA-C [0|1] rs34548322
Variant score: 0.183
Transcripts:
ESRRB:ENST00000644823.1:c.51-27891del:p.(=)
Pathogenicity Data:
Best Score: 0.382452
REMM: 0.382
Frequency Data:
gnomAD_G_AFR: 0.3109%
gnomAD_G_AMR: 1.5042%
gnomAD_G_EAS: 0.0197%
gnomAD_G_NFE: 1.5791%
gnomAD_G_SAS: 1.1792%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 14-76420587-GTGTGTGTT-G [0/1] rs1470898976
Variant score: 0.171
Transcripts:
ESRRB:ENST00000644823.1:c.51-18753_51-18746del:p.(=)
Pathogenicity Data:
Best Score: 0.267213
REMM: 0.267
Frequency Data:
gnomAD_G_AFR: 0.2675%
gnomAD_G_AMR: 1.2589%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 1.3003%
gnomAD_G_SAS: 0.5059%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76415622-T-G [0/1] rs117093624
Variant score: 0.168
Transcripts:
ESRRB:ENST00000644823.1:c.51-23719T>G:p.(=)
Pathogenicity Data:
Best Score: 0.33094
REMM: 0.331
Frequency Data:
UK10K: 1.5340%
gnomAD_G_AFR: 0.2935%
gnomAD_G_AMR: 1.4641%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.5172%
gnomAD_G_SAS: 1.1628%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76435708-G-A [0/1] rs138208230
Variant score: 0.163
Transcripts:
ESRRB:ENST00000644823.1:c.51-3633G>A:p.(=)
Pathogenicity Data:
Best Score: 0.312219
REMM: 0.312
Frequency Data:
UK10K: 1.4811%
gnomAD_G_AFR: 0.2885%
gnomAD_G_AMR: 1.4571%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.5126%
gnomAD_G_SAS: 1.2023%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76461290-C-T [0/1] rs139888489
Variant score: 0.160
Transcripts:
ESRRB:ENST00000644823.1:c.461-1255C>T:p.(=)
Pathogenicity Data:
Best Score: 0.305765
REMM: 0.306
Frequency Data:
UK10K: 1.4811%
gnomAD_G_AFR: 0.2960%
gnomAD_G_AMR: 1.4852%
gnomAD_G_EAS: 0.0386%
gnomAD_G_NFE: 1.5102%
gnomAD_G_SAS: 1.2656%
CODING_TRANSCRIPT_INTRON_VARIANT INS 14-76445684-C-CTTT [0/1] rs940535821
Variant score: 0.158
Transcripts:
ESRRB:ENST00000644823.1:c.460+5934_460+5935insTTT:p.(=)
Pathogenicity Data:
Best Score: 0.291823
REMM: 0.292
Frequency Data:
gnomAD_G_AFR: 0.2908%
gnomAD_G_AMR: 1.0886%
gnomAD_G_EAS: 0.0221%
gnomAD_G_NFE: 1.4802%
gnomAD_G_SAS: 0.4204%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76438579-G-A [0/1] rs140521905
Variant score: 0.131
Transcripts:
ESRRB:ENST00000644823.1:c.51-762G>A:p.(=)
Pathogenicity Data:
Best Score: 0.251437
REMM: 0.251
Frequency Data:
UK10K: 1.4679%
gnomAD_G_AFR: 0.2872%
gnomAD_G_AMR: 1.4496%
gnomAD_G_EAS: 0.0389%
gnomAD_G_NFE: 1.5140%
gnomAD_G_SAS: 1.2960%
INTERGENIC_VARIANT DEL 14-76358323-AAAAG-A [0/1] rs869092343
Variant score: 0.048
Transcripts:
ESRRB:ENST00000644823.1::
Pathogenicity Data:
Best Score: 0.289909
REMM: 0.290
Frequency Data:
gnomAD_G_AFR: 1.1108%
gnomAD_G_AMR: 1.5425%
gnomAD_G_EAS: 1.2131%
gnomAD_G_NFE: 1.9688%
gnomAD_G_SAS: 1.9008%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76492929-G-A [0/1]
Variant score: 0.028
Transcripts:
ESRRB:ENST00000644823.1:c.1120+1213G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0282123
REMM: 0.028
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76422809-A-C [0|1] rs144223374
Variant score: 0.028
Transcripts:
ESRRB:ENST00000644823.1:c.51-16532A>C:p.(=)
Pathogenicity Data:
Best Score: 0.0537024
REMM: 0.054
Frequency Data:
UK10K: 1.4414%
gnomAD_G_AFR: 0.2910%
gnomAD_G_AMR: 1.4644%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.5124%
gnomAD_G_SAS: 1.1811%
CODING_TRANSCRIPT_INTRON_VARIANT INS 14-76469944-C-CTTTT [0/1] rs1178018542
Variant score: 0.015
Transcripts:
ESRRB:ENST00000644823.1:c.577+7283_577+7284insTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.0261456
REMM: 0.026
Frequency Data:
gnomAD_G_AFR: 0.6724%
gnomAD_G_AMR: 0.6598%
gnomAD_G_EAS: 0.2929%
gnomAD_G_NFE: 1.4120%
gnomAD_G_SAS: 0.1988%
CODING_TRANSCRIPT_INTRON_VARIANT INS 14-76452653-C-CAAACA [0/1] rs1555399057
Variant score: 0.011
Transcripts:
ESRRB:ENST00000644823.1:c.461-9892_461-9891insAAACA:p.(=)
Pathogenicity Data:
Best Score: 0.0230607
REMM: 0.023
Frequency Data:
gnomAD_G_AFR: 0.4609%
gnomAD_G_AMR: 1.4622%
gnomAD_G_EAS: 0.0534%
gnomAD_G_NFE: 1.5827%
gnomAD_G_SAS: 1.4357%
CODING_TRANSCRIPT_INTRON_VARIANT INS 14-76452643-C-CA [0/1] rs397700387
Variant score: 0.004
Transcripts:
ESRRB:ENST00000644823.1:c.461-9902_461-9901insA:p.(=)
Pathogenicity Data:
Best Score: 0.0263063
REMM: 0.026
Frequency Data:
gnomAD_G_AFR: 0.6059%
gnomAD_G_AMR: 1.9548%
gnomAD_G_EAS: 0.0691%
gnomAD_G_NFE: 1.9757%
gnomAD_G_SAS: 1.7388%
INTERGENIC_VARIANT SNV 14-76365705-T-C [0/1]
Variant score: 0.003
Transcripts:
ESRRB:ENST00000644823.1::
Pathogenicity Data:
Best Score: 0.00276786
REMM: 0.003
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76431874-C-T [0/1] rs117185209
Variant score: 0.002
Transcripts:
ESRRB:ENST00000644823.1:c.51-7467C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00403333
REMM: 0.004
Frequency Data:
UK10K: 1.5340%
gnomAD_G_AFR: 0.2912%
gnomAD_G_AMR: 1.4700%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.5082%
gnomAD_G_SAS: 1.2038%
CODING_TRANSCRIPT_INTRON_VARIANT INS 14-76460709-A-ATTTTTTTTTTTTTTTTT [0/1] rs58597850
Variant score: 0.002
Transcripts:
ESRRB:ENST00000644823.1:c.461-1836_461-1835insTTTTTTTTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.002
REMM: 0.002
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76422805-C-T [0|1] rs145336516
Variant score: 0.002
Transcripts:
ESRRB:ENST00000644823.1:c.51-16536C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00324286
REMM: 0.003
Frequency Data:
UK10K: 1.4414%
gnomAD_G_AFR: 0.2935%
gnomAD_G_AMR: 1.4654%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.5141%
gnomAD_G_SAS: 1.1816%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76433265-G-T [0/1] rs116990304
Variant score: 0.001
Transcripts:
ESRRB:ENST00000644823.1:c.51-6076G>T:p.(=)
Pathogenicity Data:
Best Score: 0.00233333
REMM: 0.002
Frequency Data:
UK10K: 1.4943%
gnomAD_G_AFR: 0.2912%
gnomAD_G_AMR: 1.4652%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.5082%
gnomAD_G_SAS: 1.1998%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76462078-C-A [0/1] rs148091445
Variant score: 0.001
Transcripts:
ESRRB:ENST00000644823.1:c.461-467C>A:p.(=)
Pathogenicity Data:
Best Score: 0.00205556
REMM: 0.002
Frequency Data:
UK10K: 1.4546%
gnomAD_G_AFR: 0.2671%
gnomAD_G_AMR: 1.3722%
gnomAD_G_EAS: 0.0386%
gnomAD_G_NFE: 1.4232%
gnomAD_G_SAS: 1.2842%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76422171-G-A [0/1] rs141778998
Variant score: 0.001
Transcripts:
ESRRB:ENST00000644823.1:c.51-17170G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00168333
REMM: 0.002
Frequency Data:
gnomAD_G_AFR: 0.3022%
gnomAD_G_AMR: 1.4150%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 1.5069%
gnomAD_G_SAS: 1.1326%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76409317-C-G [0/1] rs117669357
Variant score: 0.001
Transcripts:
ESRRB:ENST00000644823.1:c.51-30024C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0015
REMM: 0.002
Frequency Data:
UK10K: 1.5869%
gnomAD_G_AFR: 0.2989%
gnomAD_G_AMR: 1.4731%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.5531%
gnomAD_G_SAS: 1.1860%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76423898-G-C [0/1] rs113612136
Variant score: 0.001
Transcripts:
ESRRB:ENST00000644823.1:c.51-15443G>C:p.(=)
Pathogenicity Data:
Best Score: 0.00120833
REMM: 0.001
Frequency Data:
UK10K: 1.5075%
gnomAD_G_AFR: 0.3443%
gnomAD_G_AMR: 1.4531%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 1.5102%
gnomAD_G_SAS: 1.1672%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76429147-C-A [0|1] rs150931978
Variant score: 0.001
Transcripts:
ESRRB:ENST00000644823.1:c.51-10194C>A:p.(=)
Pathogenicity Data:
Best Score: 0.001
REMM: 0.001
Frequency Data:
UK10K: 1.5340%
gnomAD_G_AFR: 0.2938%
gnomAD_G_AMR: 1.4650%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.5099%
gnomAD_G_SAS: 1.1652%
INTERGENIC_VARIANT DEL 14-76367556-CA-C [0/1]
Variant score: 0.001
Transcripts:
ESRRB:ENST00000644823.1::
Pathogenicity Data:
Best Score: 5.0E-4
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76391168-G-A [0/1] rs569974342
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.50+14717G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.0397%
gnomAD_G_AFR: 0.0457%
gnomAD_G_AMR: 0.2679%
gnomAD_G_NFE: 0.1088%
gnomAD_G_SAS: 0.1451%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76406982-C-T [0/1] rs117269542
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.50+30531C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.5075%
gnomAD_G_AFR: 0.2957%
gnomAD_G_AMR: 1.4510%
gnomAD_G_EAS: 0.0578%
gnomAD_G_NFE: 1.5095%
gnomAD_G_SAS: 0.5174%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76410786-T-A [0/1] rs184875206
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.51-28555T>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.5604%
gnomAD_G_AFR: 0.2940%
gnomAD_G_AMR: 1.4531%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.5542%
gnomAD_G_SAS: 1.2053%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76411076-G-A [0/1] rs118093958
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.51-28265G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.5604%
gnomAD_G_AFR: 0.3044%
gnomAD_G_AMR: 1.4710%
gnomAD_G_EAS: 0.0198%
gnomAD_G_NFE: 1.5558%
gnomAD_G_SAS: 1.2020%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76412175-C-T [0/1] rs145195607
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.51-27166C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.5604%
gnomAD_G_AFR: 0.9075%
gnomAD_G_AMR: 1.5039%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.5510%
gnomAD_G_SAS: 1.1628%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76415553-A-G [0/1] rs149779351
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.51-23788A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.5340%
gnomAD_G_AFR: 0.2887%
gnomAD_G_AMR: 1.4594%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.5139%
gnomAD_G_SAS: 1.1821%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 14-76419018-CT-C [0/1] rs869269538
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.51-20322del:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.7581%
gnomAD_G_AMR: 1.7181%
gnomAD_G_EAS: 0.1444%
gnomAD_G_NFE: 1.6954%
gnomAD_G_SAS: 1.9101%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76422546-T-C [0/1] rs117092224
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.51-16795T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.5340%
gnomAD_G_AFR: 0.2985%
gnomAD_G_AMR: 1.4721%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.5159%
gnomAD_G_SAS: 1.1836%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76422565-T-C [0/1] rs118042711
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.51-16776T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.5208%
gnomAD_G_AFR: 0.2960%
gnomAD_G_AMR: 1.4717%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.5158%
gnomAD_G_SAS: 1.1826%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76423058-A-G [0|1] rs148807259
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.51-16283A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.5340%
gnomAD_G_AFR: 0.2963%
gnomAD_G_AMR: 1.4729%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.5113%
gnomAD_G_SAS: 1.2028%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76423106-T-C [0/1] rs188380487
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.51-16235T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.2913%
gnomAD_G_AMR: 1.4808%
gnomAD_G_EAS: 0.0198%
gnomAD_G_NFE: 1.5263%
gnomAD_G_SAS: 1.2253%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76423205-T-G [0/1] rs192611864
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.51-16136T>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.5208%
gnomAD_G_AFR: 0.2990%
gnomAD_G_AMR: 1.4348%
gnomAD_G_EAS: 0.0205%
gnomAD_G_NFE: 1.5119%
gnomAD_G_SAS: 1.1191%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76423256-A-G [0/1] rs142452534
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.51-16085A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.5340%
gnomAD_G_AFR: 0.3071%
gnomAD_G_AMR: 1.5575%
gnomAD_G_EAS: 0.0202%
gnomAD_G_NFE: 1.5191%
gnomAD_G_SAS: 1.1945%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76423518-T-C [0/1] rs117621800
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.51-15823T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.5340%
gnomAD_G_AFR: 0.2936%
gnomAD_G_AMR: 1.4642%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.5115%
gnomAD_G_SAS: 1.1826%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76424041-T-C [0/1] rs117178008
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.51-15300T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.5340%
gnomAD_G_AFR: 0.2958%
gnomAD_G_AMR: 1.4702%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.5071%
gnomAD_G_SAS: 1.1840%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76424182-G-A [0/1] rs74068622
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.51-15159G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.5604%
gnomAD_G_AFR: 1.5019%
gnomAD_G_AMR: 1.5891%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.5453%
gnomAD_G_SAS: 1.1816%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76424893-C-T [0/1] rs149123663
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.51-14448C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.5340%
gnomAD_G_AFR: 0.2961%
gnomAD_G_AMR: 1.4715%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 1.5132%
gnomAD_G_SAS: 1.1840%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76434027-C-T [0/1] rs148617825
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.51-5314C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.5208%
gnomAD_G_AFR: 0.2925%
gnomAD_G_AMR: 1.5094%
gnomAD_G_EAS: 0.0199%
gnomAD_G_NFE: 1.5104%
gnomAD_G_SAS: 1.2257%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76437177-C-T [0/1] rs117636152
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.51-2164C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.4811%
gnomAD_G_AFR: 0.2916%
gnomAD_G_AMR: 1.4664%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 1.5164%
gnomAD_G_SAS: 1.2297%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76445339-C-T [0/1] rs143513450
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.460+5589C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.4282%
gnomAD_G_AFR: 0.2883%
gnomAD_G_AMR: 1.4423%
gnomAD_G_EAS: 0.0389%
gnomAD_G_NFE: 1.5051%
gnomAD_G_SAS: 1.3842%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76448219-G-T [0/1] rs75651769
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.460+8469G>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.4943%
gnomAD_G_AFR: 0.3047%
gnomAD_G_AMR: 1.4530%
gnomAD_G_EAS: 0.0388%
gnomAD_G_NFE: 1.5065%
gnomAD_G_SAS: 1.2687%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76456110-G-C [0/1] rs55950575
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.461-6435G>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.4150%
gnomAD_G_AFR: 0.2925%
gnomAD_G_AMR: 1.4580%
gnomAD_G_EAS: 0.0195%
gnomAD_G_NFE: 1.4795%
gnomAD_G_SAS: 0.5632%
CODING_TRANSCRIPT_INTRON_VARIANT INS 14-76458840-C-CTT [0/1] rs58084859
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.461-3705_461-3704insTT:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.3210%
gnomAD_G_AMR: 0.8124%
gnomAD_G_EAS: 0.1098%
gnomAD_G_NFE: 1.3736%
gnomAD_G_SAS: 0.7213%
CODING_TRANSCRIPT_INTRON_VARIANT INS 14-76460868-A-AT [0/1] rs34134077
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.461-1677_461-1676insT:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.3456%
gnomAD_G_AMR: 1.4692%
gnomAD_G_EAS: 0.0389%
gnomAD_G_NFE: 1.5231%
gnomAD_G_SAS: 1.2793%
CODING_TRANSCRIPT_INTRON_VARIANT INS 14-76463451-T-TTTTTTTGTTTGTTTG [0/1] rs1555342261
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.577+790_577+791insTTTTTTGTTTGTTTG:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.2801%
gnomAD_G_AMR: 1.1706%
gnomAD_G_EAS: 0.1602%
gnomAD_G_NFE: 1.4307%
gnomAD_G_SAS: 1.2212%
CODING_TRANSCRIPT_INTRON_VARIANT INS 14-76466742-C-CA [0/1] rs201787148
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.577+4081_577+4082insA:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.4546%
gnomAD_G_AFR: 0.3031%
gnomAD_G_AMR: 1.3752%
gnomAD_G_EAS: 0.1764%
gnomAD_G_NFE: 1.4607%
gnomAD_G_SAS: 0.6820%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76472351-C-G [0/1] rs565524608
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.578-9665C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_EAS: 0.0966%
gnomAD_G_SAS: 0.0414%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-76477857-G-A [0/1] rs112584326
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1:c.578-4159G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.4546%
gnomAD_G_AFR: 0.2983%
gnomAD_G_AMR: 1.3266%
gnomAD_G_EAS: 0.2319%
gnomAD_G_NFE: 1.3832%
gnomAD_G_SAS: 0.5396%
DOWNSTREAM_GENE_VARIANT SNV 14-76506489-G-A [0/1]
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1::
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 14-76519407-C-T [0/1] rs72731693
Variant score: 0.000
Transcripts:
ESRRB:ENST00000644823.1::
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.6530%
gnomAD_G_AFR: 0.5822%
gnomAD_G_AMR: 1.6540%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.5455%
gnomAD_G_SAS: 0.5394%

SLU7

Exomiser Score: 0.329 (p=1.5E-1)

Phenotype Score: 0.503

Variant Score: 0.800

Phenotype matches:
Proximity score 0.503 in interactome to CASP10 and phenotypic similarity 0.876 to Autoimmune lymphoproliferative syndrome associated with CASP10.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010619, Fibroadenoma of the breast
HP:0006625, Multifocal breast carcinoma - HP:0010619, Fibroadenoma of the breast
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.329 (p=1.5E-1)

Phenotype Score: 0.503

Variant Score: 0.800

No phenotype matches to diseases with this MOI.
Variants contributing to score:
SPLICE_REGION_VARIANT INS 5-160412523-T-TAAAAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.800 CONTRIBUTING VARIANT
Transcripts:
SLU7:ENST00000297151.9:c.571-5_571-4insTTTTT:p.?
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.158 (p=2.2E-1)

Phenotype Score: 0.503

Variant Score: 0.695

No phenotype matches to diseases with this MOI.
Variants contributing to score:
SPLICE_REGION_VARIANT INS 5-160412523-T-TAAAAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.800 CONTRIBUTING VARIANT
Transcripts:
SLU7:ENST00000297151.9:c.571-5_571-4insTTTTT:p.?
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 5-160404519-T-G [0/1] rs758206933
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.590 CONTRIBUTING VARIANT
Transcripts:
SLU7:ENST00000297151.9:c.1502A>C:p.(Lys501Thr)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_EAS: 0.0731%
gnomAD_E_NFE: 0.0034%
gnomAD_E_SAS: 0.0139%
gnomAD_G_EAS: 0.1156%
gnomAD_G_NFE: 0.0074%
gnomAD_G_SAS: 0.0207%

LMX1B

Exomiser Score: 0.325 (p=1.5E-1)

Phenotype Score: 0.505

Variant Score: 0.796

Phenotype matches:
Phenotypic similarity 0.444 to Nail-patella syndrome associated with LMX1B.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000767, Pectus excavatum
HP:0006625, Multifocal breast carcinoma - HP:0000767, Pectus excavatum
Phenotypic similarity 0.312 to mouse mutant involving LMX1B.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000077, abnormal interparietal bone morphology
HP:0006625, Multifocal breast carcinoma - MP:0000077, abnormal interparietal bone morphology
Proximity score 0.505 in interactome to OTX2 and phenotypic similarity 0.676 to Combined pituitary hormone deficiencies, genetic forms associated with OTX2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
HP:0006625, Multifocal breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
Proximity score 0.505 in interactome to OTX2 and phenotypic similarity 0.338 to mouse mutant of OTX2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000438, abnormal cranium morphology
HP:0006625, Multifocal breast carcinoma - MP:0000438, abnormal cranium morphology
Proximity score 0.505 in interactome to OTX2 and phenotypic similarity 0.244 to fish mutant of OTX2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0007773, mandibular arch skeleton shortened, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0007773, mandibular arch skeleton shortened, abnormal
Known diseases:
OMIM:161200 Nail-patella syndrome - autosomal dominant
OMIM:256020 Focal segmental glomerulosclerosis 10 - autosomal recessive
ORPHA:2613 Nail-patella-like renal disease - autosomal recessive
ORPHA:2614 Nail-patella syndrome - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.325 (p=1.5E-1)

Phenotype Score: 0.505

Variant Score: 0.796

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.444 to ORPHA:2614 Nail-patella syndrome
Phenotypic similarity 0.422 to OMIM:161200 Nail-patella syndrome
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-126692695-G-A [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.796 CONTRIBUTING VARIANT
Transcripts:
LMX1B:ENST00000373474.9:c.560-447G>A:p.(=)
Pathogenicity Data:
Best Score: 0.795923
REMM: 0.796
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.301 (p=1.6E-1)

Phenotype Score: 0.505

Variant Score: 0.784

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-126692695-G-A [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.796 CONTRIBUTING VARIANT
Transcripts:
LMX1B:ENST00000373474.9:c.560-447G>A:p.(=)
Pathogenicity Data:
Best Score: 0.795923
REMM: 0.796
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-126644037-G-C [0/1] rs139505139
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.771 CONTRIBUTING VARIANT
Transcripts:
LMX1B:ENST00000373474.9:c.326+28468G>C:p.(=)
Pathogenicity Data:
Best Score: 0.78226
REMM: 0.782
Frequency Data:
gnomAD_G_AFR: 0.0072%
gnomAD_G_AMR: 0.0065%
gnomAD_G_NFE: 0.0970%
gnomAD_G_SAS: 0.0414%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-126625964-C-T [0/1] rs563942297
Variant score: 0.633
Transcripts:
LMX1B:ENST00000373474.9:c.326+10395C>T:p.(=)
Pathogenicity Data:
Best Score: 0.646536
REMM: 0.647
Frequency Data:
gnomAD_G_AFR: 0.0096%
gnomAD_G_AMR: 0.0392%
gnomAD_G_NFE: 0.1441%
gnomAD_G_SAS: 0.0829%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 9-126653142-CTT-C [0/1] rs5900715
Variant score: 0.490
Transcripts:
LMX1B:ENST00000373474.9:c.326+37574_326+37575del:p.(=)
Pathogenicity Data:
Best Score: 0.49045
REMM: 0.490
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 9-126653142-CTTT-C [0/1] rs5900715
Variant score: 0.490
Transcripts:
LMX1B:ENST00000373474.9:c.326+37574_326+37576del:p.(=)
Pathogenicity Data:
Best Score: 0.49045
REMM: 0.490
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-126670519-G-A [0/1] rs138450342
Variant score: 0.485
Transcripts:
LMX1B:ENST00000373474.9:c.327-20317G>A:p.(=)
Pathogenicity Data:
Best Score: 0.818692
REMM: 0.819
Frequency Data:
UK10K: 1.3885%
gnomAD_G_AFR: 0.2430%
gnomAD_G_AMR: 0.8166%
gnomAD_G_NFE: 1.3788%
gnomAD_G_SAS: 0.3311%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-126660172-T-G [0/1] rs10987398
Variant score: 0.414
Transcripts:
LMX1B:ENST00000373474.9:c.327-30664T>G:p.(=)
Pathogenicity Data:
Best Score: 0.456759
REMM: 0.457
Frequency Data:
gnomAD_G_AFR: 0.2751%
gnomAD_G_AMR: 0.2623%
gnomAD_G_EAS: 0.1031%
gnomAD_G_NFE: 0.5276%
gnomAD_G_SAS: 0.1704%
DOWNSTREAM_GENE_VARIANT SNV 9-126705362-G-C [0/1] rs187567896
Variant score: 0.075
Transcripts:
LMX1B:ENST00000373474.9::
Pathogenicity Data:
Best Score: 0.245403
REMM: 0.245
Frequency Data:
UK10K: 1.6530%
gnomAD_G_AFR: 0.3030%
gnomAD_G_AMR: 1.2881%
gnomAD_G_NFE: 1.8114%
gnomAD_G_SAS: 0.2277%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-126660009-G-A [0|1] rs77764274
Variant score: 0.062
Transcripts:
LMX1B:ENST00000373474.9:c.327-30827G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0619806
REMM: 0.062
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-126660140-A-G [0/1] rs376852835
Variant score: 0.049
Transcripts:
LMX1B:ENST00000373474.9:c.327-30696A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0493583
REMM: 0.049
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-126659972-C-G [0|1] rs11790342
Variant score: 0.049
Transcripts:
LMX1B:ENST00000373474.9:c.327-30864C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0490643
REMM: 0.049
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-126659986-C-G [0|1]
Variant score: 0.047
Transcripts:
LMX1B:ENST00000373474.9:c.327-30850C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0465008
REMM: 0.047
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-126660012-A-G [0|1] rs75300867
Variant score: 0.046
Transcripts:
LMX1B:ENST00000373474.9:c.327-30824A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0462956
REMM: 0.046
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-126659958-G-A [0|1] rs10987388
Variant score: 0.045
Transcripts:
LMX1B:ENST00000373474.9:c.327-30878G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0450976
REMM: 0.045
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-126659977-A-G [0|1] rs778990279
Variant score: 0.044
Transcripts:
LMX1B:ENST00000373474.9:c.327-30859A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0444504
REMM: 0.044
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-126660161-A-G [0/1] rs10987397
Variant score: 0.040
Transcripts:
LMX1B:ENST00000373474.9:c.327-30675A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0399643
REMM: 0.040
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-126660156-T-C [0/1] rs1199979612
Variant score: 0.039
Transcripts:
LMX1B:ENST00000373474.9:c.327-30680T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0392143
REMM: 0.039
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-126660154-C-T [0/1] rs10987396
Variant score: 0.036
Transcripts:
LMX1B:ENST00000373474.9:c.327-30682C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0377143
REMM: 0.038
Frequency Data:
gnomAD_G_AFR: 0.2904%
gnomAD_G_AMR: 0.1890%
gnomAD_G_EAS: 0.0275%
gnomAD_G_NFE: 0.2753%
gnomAD_G_SAS: 0.1443%
INTERGENIC_VARIANT INS 9-126715492-G-GAGGAAGGAAGGA [0/1] rs772540934
Variant score: 0.001
Transcripts:
LMX1B:ENST00000373474.9::
Pathogenicity Data:
Best Score: 0.001
REMM: 0.001
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 9-126599019-C-A [0/1] rs139919594
Variant score: 0.000
Transcripts:
LMX1B:ENST00000373474.9::
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0261%
gnomAD_G_NFE: 0.1058%
gnomAD_G_SAS: 0.0621%

MARS1

Exomiser Score: 0.325 (p=1.5E-1)

Phenotype Score: 0.501

Variant Score: 0.800

Phenotype matches:
Phenotypic similarity 0.227 to zebrafish mutant involving MARS1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0000132, ceratohyal cartilage malformed, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0000132, ceratohyal cartilage malformed, abnormal
Proximity score 0.501 in interactome to SLC6A17 and phenotypic similarity 0.998 to Progressive essential tremor-speech impairment-facial dysmorphism-intellectual disability-abnormal behavior syndrome associated with SLC6A17.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Known diseases:
OMIM:615486 Interstitial lung and liver disease - autosomal recessive
OMIM:616280 Charcot-Marie-Tooth disease, axonal, type 2U - autosomal dominant
OMIM:619692 ?Trichothiodystrophy 9, nonphotosensitive (unconfirmed)
OMIM:620323 Spastic paraplegia 70, autosomal recessive - autosomal recessive
ORPHA:401835 Autosomal recessive spastic paraplegia type 70 - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.325 (p=1.5E-1)

Phenotype Score: 0.501

Variant Score: 0.800

No phenotype matches to diseases with this MOI.
Variants contributing to score:
SPLICE_REGION_VARIANT SNV 12-57490533-T-A [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.800 CONTRIBUTING VARIANT
Transcripts:
MARS1:ENST00000262027.10:c.664-5T>A:p.?
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.160 (p=2.2E-1)

Phenotype Score: 0.501

Variant Score: 0.699

No phenotype matches to diseases with this MOI.
Variants contributing to score:
SPLICE_REGION_VARIANT SNV 12-57490533-T-A [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.800 CONTRIBUTING VARIANT
Transcripts:
MARS1:ENST00000262027.10:c.664-5T>A:p.?
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 12-57490608-A-G [0/1] rs778753999
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:3, LB:1)
Variant score: 0.598 CONTRIBUTING VARIANT
Transcripts:
MARS1:ENST00000262027.10:c.734A>G:p.(Glu245Gly)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AMR: 0.0045%
gnomAD_E_NFE: 0.0060%
gnomAD_E_SAS: 0.0209%
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0066%
gnomAD_G_NFE: 0.0118%
gnomAD_G_SAS: 0.0207%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-57493398-ATATATGT-A [0/1]
Variant score: 0.144
Transcripts:
MARS1:ENST00000262027.10:c.770+2755_770+2761del:p.(=)
Pathogenicity Data:
Best Score: 0.143606
REMM: 0.144
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-57493439-T-A [1/1]
Variant score: 0.086
Transcripts:
MARS1:ENST00000262027.10:c.770+2795T>A:p.(=)
Pathogenicity Data:
Best Score: 0.0855607
REMM: 0.086
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-57493495-TTATAATA-T [1/1]
Variant score: 0.046
Transcripts:
MARS1:ENST00000262027.10:c.770+2852_770+2858del:p.(=)
Pathogenicity Data:
Best Score: 0.0458151
REMM: 0.046
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-57493689-T-C [1/1] rs367740570
Variant score: 0.010
Transcripts:
MARS1:ENST00000262027.10:c.770+3045T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0100627
REMM: 0.010
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-57493729-T-A [1/1] rs796393626
Variant score: 0.007
Transcripts:
MARS1:ENST00000262027.10:c.770+3085T>A:p.(=)
Pathogenicity Data:
Best Score: 0.00684603
REMM: 0.007
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-57493704-AATATATT-A [1/1] rs1245262105
Variant score: 0.006
Transcripts:
MARS1:ENST00000262027.10:c.770+3061_770+3067del:p.(=)
Pathogenicity Data:
Best Score: 0.0113405
REMM: 0.011
Frequency Data:
gnomAD_G_AFR: 1.4344%
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-57493835-A-AAT [1/1]
Variant score: 0.006
Transcripts:
MARS1:ENST00000262027.10:c.770+3191_770+3192insAT:p.(=)
Pathogenicity Data:
Best Score: 0.00566349
REMM: 0.006
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-57493836-T-A [1/1] rs796940126
Variant score: 0.006
Transcripts:
MARS1:ENST00000262027.10:c.770+3192T>A:p.(=)
Pathogenicity Data:
Best Score: 0.00566349
REMM: 0.006
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-57493750-C-T [1/1]
Variant score: 0.005
Transcripts:
MARS1:ENST00000262027.10:c.770+3106C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00484603
REMM: 0.005
Frequency Data:
No frequency data

MEF2C

Exomiser Score: 0.323 (p=1.5E-1)

Phenotype Score: 0.510

Variant Score: 0.789

Phenotype matches:
Phenotypic similarity 0.277 to mouse mutant involving MEF2C.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0008278, failure of sternum ossification
HP:0006625, Multifocal breast carcinoma - MP:0008278, failure of sternum ossification
Phenotypic similarity 0.281 to zebrafish mutant involving MEF2C.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0000935, ceratohyal-branchiostegal ray joint morphology, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0000935, ceratohyal-branchiostegal ray joint morphology, abnormal
Proximity score 0.510 in interactome to TWIST2 and phenotypic similarity 0.635 to Barber-Say syndrome associated with TWIST2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0100783, Breast aplasia
HP:0006625, Multifocal breast carcinoma - HP:0100783, Breast aplasia
Proximity score 0.510 in interactome to TWIST2 and phenotypic similarity 0.306 to mouse mutant of TWIST2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0008395, abnormal osteoblast differentiation
HP:0006625, Multifocal breast carcinoma - MP:0008395, abnormal osteoblast differentiation
Known diseases:
OMIM:613443 Chromosome 5q14.3 deletion syndrome (CNV)
OMIM:613443 Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language - autosomal dominant
ORPHA:228384 5q14.3 microdeletion syndrome (CNV)
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.323 (p=1.5E-1)

Phenotype Score: 0.510

Variant Score: 0.789

No phenotype matches to diseases with this MOI.
Variants contributing to score:
FIVE_PRIME_UTR_INTRON_VARIANT DEL 5-88873708-ATTTTTTTTT-A [0/1] rs199642010
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.789 CONTRIBUTING VARIANT
Transcripts:
MEF2C:ENST00000504921.7:c.-143+9238_-143+9246del:p.(=)
Pathogenicity Data:
Best Score: 0.789257
REMM: 0.789
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.033 (p=3.6E-1)

Phenotype Score: 0.255

Variant Score: 0.789

No phenotype matches to diseases with this MOI.
Variants contributing to score:
FIVE_PRIME_UTR_INTRON_VARIANT DEL 5-88873708-ATTTTTTT-A [0/1] rs199642010
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.789 CONTRIBUTING VARIANT
Transcripts:
MEF2C:ENST00000504921.7:c.-143+9240_-143+9246del:p.(=)
Pathogenicity Data:
Best Score: 0.789257
REMM: 0.789
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT DEL 5-88873708-ATTTTTTTTT-A [0/1] rs199642010
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.789 CONTRIBUTING VARIANT
Transcripts:
MEF2C:ENST00000504921.7:c.-143+9238_-143+9246del:p.(=)
Pathogenicity Data:
Best Score: 0.789257
REMM: 0.789
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT INS 5-88747333-C-CT [0/1]
Variant score: 0.270
Transcripts:
MEF2C:ENST00000504921.7:c.637+1736_637+1737insA:p.(=)
Pathogenicity Data:
Best Score: 0.27023
REMM: 0.270
Frequency Data:
No frequency data
REGULATORY_REGION_VARIANT DEL 5-90017904-GTTTT-G [0/1] rs138395949
Variant score: 0.221
Transcripts:
MEF2C:ENST00000504921.7::
MEF2C:ENST00000283122.8::
Pathogenicity Data:
Best Score: 0.221244
REMM: 0.221
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT DEL 5-88869294-TACAC-T [1/1] rs1391800642
Variant score: 0.085
Transcripts:
MEF2C:ENST00000504921.7:c.-143+13657_-143+13660del:p.(=)
Pathogenicity Data:
Best Score: 0.134804
REMM: 0.135
Frequency Data:
gnomAD_G_AFR: 0.6937%
gnomAD_G_AMR: 1.0950%
gnomAD_G_EAS: 0.4108%
gnomAD_G_NFE: 1.3117%
gnomAD_G_SAS: 0.6233%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 5-88797455-CT-C [1|0] rs879036291
Variant score: 0.018
Transcripts:
MEF2C:ENST00000504921.7:c.258+7142del:p.(=)
Pathogenicity Data:
Best Score: 0.0289817
REMM: 0.029
Frequency Data:
gnomAD_G_AFR: 0.7786%
gnomAD_G_AMR: 0.5441%
gnomAD_G_EAS: 0.0966%
gnomAD_G_NFE: 0.3507%
gnomAD_G_SAS: 1.3645%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-88762583-A-T [0/1] rs1042877491
Variant score: 0.002
Transcripts:
MEF2C:ENST00000504921.7:c.259-1255T>A:p.(=)
Pathogenicity Data:
Best Score: 0.00199444
REMM: 0.002
Frequency Data:
gnomAD_G_AFR: 0.0170%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 0.0162%

NRG3

Exomiser Score: 0.310 (p=1.5E-1)

Phenotype Score: 0.502

Variant Score: 0.791

Phenotype matches:
Proximity score 0.502 in interactome to DYRK1A and phenotypic similarity 0.618 to DYRK1A-related intellectual disability syndrome due to 21q22.13q22.2 microdeletion associated with DYRK1A.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0100783, Breast aplasia
HP:0006625, Multifocal breast carcinoma - HP:0100783, Breast aplasia
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.310 (p=1.5E-1)

Phenotype Score: 0.502

Variant Score: 0.791

No phenotype matches to diseases with this MOI.
Variants contributing to score:
UPSTREAM_GENE_VARIANT SNV 10-81875122-G-T [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.791 CONTRIBUTING VARIANT
Transcripts:
NRG3:ENST00000372141.7::
Pathogenicity Data:
Best Score: 0.791409
REMM: 0.791
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.174 (p=2.1E-1)

Phenotype Score: 0.502

Variant Score: 0.709

No phenotype matches to diseases with this MOI.
Variants contributing to score:
UPSTREAM_GENE_VARIANT SNV 10-81875122-G-T [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.791 CONTRIBUTING VARIANT
Transcripts:
NRG3:ENST00000372141.7::
Pathogenicity Data:
Best Score: 0.791409
REMM: 0.791
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82197272-A-G [0/1] rs1269739323
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.626 CONTRIBUTING VARIANT
Transcripts:
NRG3:ENST00000372141.7:c.824-161467A>G:p.(=)
Pathogenicity Data:
Best Score: 0.627599
REMM: 0.628
Frequency Data:
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0131%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 10-82682946-ATT-A [0/1] rs71009814
Variant score: 0.555
Transcripts:
NRG3:ENST00000372141.7:c.954-55630_954-55629del:p.(=)
Pathogenicity Data:
Best Score: 0.555319
REMM: 0.555
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82424160-G-A [0/1] rs991252600
Variant score: 0.548
Transcripts:
NRG3:ENST00000372141.7:c.953+65292G>A:p.(=)
Pathogenicity Data:
Best Score: 0.551319
REMM: 0.551
Frequency Data:
gnomAD_G_NFE: 0.0044%
gnomAD_G_SAS: 0.0415%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82525621-T-C [0/1] rs189699182
Variant score: 0.503
Transcripts:
NRG3:ENST00000372141.7:c.953+166753T>C:p.(=)
Pathogenicity Data:
Best Score: 0.559663
REMM: 0.560
Frequency Data:
UK10K: 0.5554%
gnomAD_G_AFR: 0.0603%
gnomAD_G_AMR: 0.3475%
gnomAD_G_NFE: 0.4781%
gnomAD_G_SAS: 0.1243%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82560918-T-A [0/1] rs1412053136
Variant score: 0.497
Transcripts:
NRG3:ENST00000372141.7:c.954-177659T>A:p.(=)
Pathogenicity Data:
Best Score: 0.497309
REMM: 0.497
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82962579-C-T [0/1] rs758227462
Variant score: 0.468
Transcripts:
NRG3:ENST00000372141.7:c.1284+3504C>T:p.(=)
Pathogenicity Data:
Best Score: 0.468837
REMM: 0.469
Frequency Data:
UK10K: 0.0132%
gnomAD_G_NFE: 0.0044%
CODING_TRANSCRIPT_INTRON_VARIANT INS 10-82491293-A-AATATATATATATATATATACATATATATATATATATATATATACATAT [0/1]
Variant score: 0.454
Transcripts:
NRG3:ENST00000372141.7:c.953+132425_953+132426insATATATATATATATATATACATATATATATATATATATATATACATAT:p.(=)
Pathogenicity Data:
Best Score: 0.454164
REMM: 0.454
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82712502-C-T [0/1] rs145916914
Variant score: 0.449
Transcripts:
NRG3:ENST00000372141.7:c.954-26075C>T:p.(=)
Pathogenicity Data:
Best Score: 0.46967
REMM: 0.470
Frequency Data:
UK10K: 0.1719%
gnomAD_G_AFR: 0.0217%
gnomAD_G_AMR: 0.0588%
gnomAD_G_NFE: 0.2867%
gnomAD_G_SAS: 0.2692%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 10-82426597-AATTATTATTATTATTATTATT-A [0/1]
Variant score: 0.439
Transcripts:
NRG3:ENST00000372141.7:c.953+67730_953+67750del:p.(=)
Pathogenicity Data:
Best Score: 0.439009
REMM: 0.439
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 10-82527172-CA-C [0/1] rs549869379
Variant score: 0.438
Transcripts:
NRG3:ENST00000372141.7:c.953+168305del:p.(=)
Pathogenicity Data:
Best Score: 0.438489
REMM: 0.438
Frequency Data:
gnomAD_G_AFR: 0.0025%
gnomAD_G_NFE: 0.0135%
INTERGENIC_VARIANT DEL 10-83006654-AAAAT-A [0/1] rs4034739
Variant score: 0.428
Transcripts:
NRG3:ENST00000372141.7::
Pathogenicity Data:
Best Score: 0.428032
REMM: 0.428
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 10-82660196-CAAAAAAAAAAAAAAA-C [0/1]
Variant score: 0.416
Transcripts:
NRG3:ENST00000372141.7:c.954-78380_954-78366del:p.(=)
Pathogenicity Data:
Best Score: 0.416099
REMM: 0.416
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82619116-C-G [0/1] rs189391210
Variant score: 0.391
Transcripts:
NRG3:ENST00000372141.7:c.954-119461C>G:p.(=)
Pathogenicity Data:
Best Score: 0.439195
REMM: 0.439
Frequency Data:
UK10K: 0.5951%
gnomAD_G_AFR: 0.0920%
gnomAD_G_AMR: 0.1772%
gnomAD_G_NFE: 0.5730%
gnomAD_G_SAS: 0.0836%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82324212-T-C [0/1] rs1015823004
Variant score: 0.383
Transcripts:
NRG3:ENST00000372141.7:c.824-34527T>C:p.(=)
Pathogenicity Data:
Best Score: 0.384749
REMM: 0.385
Frequency Data:
gnomAD_G_NFE: 0.0044%
gnomAD_G_SAS: 0.0414%
CODING_TRANSCRIPT_INTRON_VARIANT INS 10-82707846-T-TAAAA [0/1] rs373670610
Variant score: 0.267
Transcripts:
NRG3:ENST00000372141.7:c.954-30731_954-30730insAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.266596
REMM: 0.267
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 10-82522039-CT-C [1/1] rs71009811
Variant score: 0.257
Transcripts:
NRG3:ENST00000372141.7:c.953+163172del:p.(=)
Pathogenicity Data:
Best Score: 0.257133
REMM: 0.257
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 10-81915496-G-GTTTTTTTTTTT [0/1] rs78693924
Variant score: 0.248
Transcripts:
NRG3:ENST00000372141.7:c.823+39333_823+39334insTTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.2483
REMM: 0.248
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 10-82761922-C-CTCTTTCTTTCTTTCTT [0/1]
Variant score: 0.248
Transcripts:
NRG3:ENST00000372141.7:c.1027+23272_1027+23273insTCTTTCTTTCTTTCTT:p.(=)
Pathogenicity Data:
Best Score: 0.247858
REMM: 0.248
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 10-82495811-G-GACACACACACACACACAC [0/1] rs55671097
Variant score: 0.244
Transcripts:
NRG3:ENST00000372141.7:c.953+136943_953+136944insACACACACACACACACAC:p.(=)
Pathogenicity Data:
Best Score: 0.343259
REMM: 0.343
Frequency Data:
gnomAD_G_AFR: 0.2457%
gnomAD_G_AMR: 0.4365%
gnomAD_G_EAS: 0.1237%
gnomAD_G_NFE: 1.1457%
gnomAD_G_SAS: 0.6100%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 10-82649459-CT-C [1/1] rs71469930
Variant score: 0.168
Transcripts:
NRG3:ENST00000372141.7:c.954-89117del:p.(=)
Pathogenicity Data:
Best Score: 0.168202
REMM: 0.168
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82043590-T-C [0/1] rs4933821
Variant score: 0.133
Transcripts:
NRG3:ENST00000372141.7:c.823+167427T>C:p.(=)
Pathogenicity Data:
Best Score: 0.555551
REMM: 0.556
Frequency Data:
UK10K: 1.8910%
gnomAD_G_AFR: 0.2480%
gnomAD_G_AMR: 0.8396%
gnomAD_G_NFE: 1.8188%
gnomAD_G_SAS: 0.3317%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 10-82046781-GT-G [1/1] rs201031439
Variant score: 0.097
Transcripts:
NRG3:ENST00000372141.7:c.823+170619del:p.(=)
Pathogenicity Data:
Best Score: 0.097354
REMM: 0.097
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82046801-G-A [1/1] rs4255486
Variant score: 0.097
Transcripts:
NRG3:ENST00000372141.7:c.823+170638G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0967016
REMM: 0.097
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82046606-T-A [0/1] rs76414209
Variant score: 0.087
Transcripts:
NRG3:ENST00000372141.7:c.823+170443T>A:p.(=)
Pathogenicity Data:
Best Score: 0.0871329
REMM: 0.087
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 10-82545783-CT-C [0/1] rs1002975772
Variant score: 0.079
Transcripts:
NRG3:ENST00000372141.7:c.953+186916del:p.(=)
Pathogenicity Data:
Best Score: 0.0794548
REMM: 0.079
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82884011-T-C [0/1] rs193107829
Variant score: 0.069
Transcripts:
NRG3:ENST00000372141.7:c.1054+18574T>C:p.(=)
Pathogenicity Data:
Best Score: 0.341023
REMM: 0.341
Frequency Data:
UK10K: 0.7405%
gnomAD_G_AFR: 0.1756%
gnomAD_G_AMR: 1.9321%
gnomAD_G_NFE: 0.7417%
gnomAD_G_SAS: 0.7887%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82046295-A-G [1|1] rs191742951
Variant score: 0.068
Transcripts:
NRG3:ENST00000372141.7:c.823+170132A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0683175
REMM: 0.068
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82046283-T-C [1|1] rs188513111
Variant score: 0.066
Transcripts:
NRG3:ENST00000372141.7:c.823+170120T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0664964
REMM: 0.066
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 10-82046741-C-CTTTA [1|1] rs1341946253
Variant score: 0.058
Transcripts:
NRG3:ENST00000372141.7:c.823+170578_823+170579insTTTA:p.(=)
Pathogenicity Data:
Best Score: 0.0575837
REMM: 0.058
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 10-82993288-CAAA-C [0/1]
Variant score: 0.057
Transcripts:
NRG3:ENST00000372141.7::
Pathogenicity Data:
Best Score: 0.0574881
REMM: 0.057
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 10-82721123-CTT-C [0/1] rs531541747
Variant score: 0.055
Transcripts:
NRG3:ENST00000372141.7:c.954-17453_954-17452del:p.(=)
Pathogenicity Data:
Best Score: 0.0546008
REMM: 0.055
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82046490-T-G [1/1]
Variant score: 0.049
Transcripts:
NRG3:ENST00000372141.7:c.823+170327T>G:p.(=)
Pathogenicity Data:
Best Score: 0.0489143
REMM: 0.049
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 10-82046736-ATGTC-A [1|1] rs1310720997
Variant score: 0.047
Transcripts:
NRG3:ENST00000372141.7:c.823+170574_823+170577del:p.(=)
Pathogenicity Data:
Best Score: 0.0468429
REMM: 0.047
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82089541-A-G [0/1] rs10490936
Variant score: 0.035
Transcripts:
NRG3:ENST00000372141.7:c.823+213378A>G:p.(=)
Pathogenicity Data:
Best Score: 0.181965
REMM: 0.182
Frequency Data:
UK10K: 1.9439%
gnomAD_G_AFR: 0.2526%
gnomAD_G_AMR: 0.7979%
gnomAD_G_NFE: 1.8436%
gnomAD_G_SAS: 0.3521%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82045210-A-G [1/1] rs9664353
Variant score: 0.033
Transcripts:
NRG3:ENST00000372141.7:c.823+169047A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0330286
REMM: 0.033
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82046313-A-G [1|1]
Variant score: 0.026
Transcripts:
NRG3:ENST00000372141.7:c.823+170150A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0256313
REMM: 0.026
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82046385-G-A [1|1] rs201821189
Variant score: 0.025
Transcripts:
NRG3:ENST00000372141.7:c.823+170222G>A:p.(=)
Pathogenicity Data:
Best Score: 0.025206
REMM: 0.025
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82045755-A-G [1|1] rs11528180
Variant score: 0.025
Transcripts:
NRG3:ENST00000372141.7:c.823+169592A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0248
REMM: 0.025
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82045754-A-C [1|1]
Variant score: 0.024
Transcripts:
NRG3:ENST00000372141.7:c.823+169591A>C:p.(=)
Pathogenicity Data:
Best Score: 0.0243
REMM: 0.024
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82046406-G-T [1|1] rs200148294
Variant score: 0.018
Transcripts:
NRG3:ENST00000372141.7:c.823+170243G>T:p.(=)
Pathogenicity Data:
Best Score: 0.0183183
REMM: 0.018
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82045721-T-A [1/1]
Variant score: 0.017
Transcripts:
NRG3:ENST00000372141.7:c.823+169558T>A:p.(=)
Pathogenicity Data:
Best Score: 0.017221
REMM: 0.017
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82046579-T-G [1/1] rs75078123
Variant score: 0.017
Transcripts:
NRG3:ENST00000372141.7:c.823+170416T>G:p.(=)
Pathogenicity Data:
Best Score: 0.0166206
REMM: 0.017
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82046568-T-C [1/1] rs76252773
Variant score: 0.015
Transcripts:
NRG3:ENST00000372141.7:c.823+170405T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0146206
REMM: 0.015
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82045280-A-C [1/1]
Variant score: 0.013
Transcripts:
NRG3:ENST00000372141.7:c.823+169117A>C:p.(=)
Pathogenicity Data:
Best Score: 0.0127698
REMM: 0.013
Frequency Data:
No frequency data
DOWNSTREAM_GENE_VARIANT SNV 10-82989400-C-G [0/1] rs149753109
Variant score: 0.011
Transcripts:
NRG3:ENST00000372141.7::
Pathogenicity Data:
Best Score: 0.0107706
REMM: 0.011
Frequency Data:
gnomAD_G_NFE: 0.0044%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 10-82306703-TAAAA-T [0/1] rs71009805
Variant score: 0.009
Transcripts:
NRG3:ENST00000372141.7:c.824-52035_824-52032del:p.(=)
Pathogenicity Data:
Best Score: 0.0089496
REMM: 0.009
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 10-82362079-C-CA [0/1] rs58975630
Variant score: 0.004
Transcripts:
NRG3:ENST00000372141.7:c.953+3211_953+3212insA:p.(=)
Pathogenicity Data:
Best Score: 0.00674127
REMM: 0.007
Frequency Data:
gnomAD_G_AFR: 0.2779%
gnomAD_G_AMR: 0.4335%
gnomAD_G_EAS: 0.3704%
gnomAD_G_NFE: 1.3638%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 10-82479664-CA-C [0/1]
Variant score: 0.001
Transcripts:
NRG3:ENST00000372141.7:c.953+120797del:p.(=)
Pathogenicity Data:
Best Score: 0.001
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82045252-C-T [1|1] rs9663667
Variant score: 0.000
Transcripts:
NRG3:ENST00000372141.7:c.823+169089C>T:p.(=)
Pathogenicity Data:
Best Score: 4.33333E-4
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82045253-A-G [1|1] rs9664355
Variant score: 0.000
Transcripts:
NRG3:ENST00000372141.7:c.823+169090A>G:p.(=)
Pathogenicity Data:
Best Score: 4.33333E-4
REMM: 0.000
Frequency Data:
No frequency data
DOWNSTREAM_GENE_VARIANT SNV 10-82987783-G-T [0/1] rs1406460833
Variant score: 0.000
Transcripts:
NRG3:ENST00000372141.7::
Pathogenicity Data:
Best Score: 2.0E-4
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.2938%
gnomAD_G_AMR: 0.4306%
gnomAD_G_EAS: 0.0789%
gnomAD_G_NFE: 0.4933%
gnomAD_G_SAS: 0.2953%
DOWNSTREAM_GENE_VARIANT SNV 10-82988078-C-T [0/1] rs144222597
Variant score: 0.000
Transcripts:
NRG3:ENST00000372141.7::
Pathogenicity Data:
Best Score: 1.0E-4
REMM: 0.000
Frequency Data:
UK10K: 1.4414%
gnomAD_G_AFR: 0.2603%
gnomAD_G_AMR: 0.5499%
gnomAD_G_EAS: 0.0387%
gnomAD_G_NFE: 1.5811%
gnomAD_G_SAS: 0.2490%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82877562-G-T [1/1] rs2475798
Variant score: 0.000
Transcripts:
NRG3:ENST00000372141.7:c.1054+12125G>T:p.(=)
Pathogenicity Data:
Best Score: 1.95695E-6
REMM: 0.000
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 10-81859842-G-A [1|0] rs189767276
Variant score: 0.000
Transcripts:
NRG3:ENST00000372141.7::
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.6927%
gnomAD_G_AFR: 0.2988%
gnomAD_G_AMR: 0.6867%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.6122%
gnomAD_G_SAS: 0.6432%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82041483-T-G [0|1] rs776440713
Variant score: 0.000
Transcripts:
NRG3:ENST00000372141.7:c.823+165320T>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AMR: 0.0066%
gnomAD_G_NFE: 0.0029%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82148573-G-A [0/1] rs1037281592
Variant score: 0.000
Transcripts:
NRG3:ENST00000372141.7:c.824-210166G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0217%
gnomAD_G_NFE: 0.0059%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 10-82201196-CA-C [1/1] rs35232518
Variant score: 0.000
Transcripts:
NRG3:ENST00000372141.7:c.824-157542del:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82268778-G-A [0/1] rs181923242
Variant score: 0.000
Transcripts:
NRG3:ENST00000372141.7:c.824-89961G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.4893%
gnomAD_G_AFR: 0.0578%
gnomAD_G_AMR: 0.1507%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 0.5457%
gnomAD_G_SAS: 0.1662%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82522879-C-G [0/1] rs141649637
Variant score: 0.000
Transcripts:
NRG3:ENST00000372141.7:c.953+164011C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.5554%
gnomAD_G_AFR: 0.0602%
gnomAD_G_AMR: 0.3534%
gnomAD_G_NFE: 0.4751%
gnomAD_G_SAS: 0.1244%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82666650-G-A [0/1] rs140082910
Variant score: 0.000
Transcripts:
NRG3:ENST00000372141.7:c.954-71927G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.1587%
gnomAD_G_AFR: 0.0337%
gnomAD_G_AMR: 0.3927%
gnomAD_G_NFE: 0.5088%
gnomAD_G_SAS: 0.1242%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-82867882-G-A [0/1] rs1340627201
Variant score: 0.000
Transcripts:
NRG3:ENST00000372141.7:c.1054+2445G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0024%
gnomAD_G_NFE: 0.0015%

ORC6

Exomiser Score: 0.305 (p=1.5E-1)

Phenotype Score: 0.594

Variant Score: 0.685

Phenotype matches:
Phenotypic similarity 0.594 to Ear-patella-short stature syndrome associated with ORC6.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0100783, Breast aplasia
HP:0006625, Multifocal breast carcinoma - HP:0100783, Breast aplasia
Proximity score 0.504 in interactome to ORC4 and phenotypic similarity 0.620 to Meier-Gorlin syndrome 2 associated with ORC4.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003187, Breast hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0003187, Breast hypoplasia
Known diseases:
OMIM:613803 Meier-Gorlin syndrome 3 - autosomal recessive
ORPHA:2554 Ear-patella-short stature syndrome - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.305 (p=1.5E-1)

Phenotype Score: 0.594

Variant Score: 0.685

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.594 to ORPHA:2554 Ear-patella-short stature syndrome
Phenotypic similarity 0.577 to OMIM:613803 Meier-Gorlin syndrome 3
Variants contributing to score:
FIVE_PRIME_UTR_EXON_VARIANT SNV 16-46689659-G-A [0/1] rs144065502
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:1, LB:2, B:1)
Variant score: 0.712 CONTRIBUTING VARIANT
Transcripts:
ORC6:ENST00000219097.7:c.-47G>A:p.(=)
Pathogenicity Data:
Best Score: 0.830713
REMM: 0.831
Frequency Data:
UK10K: 0.2645%
gnomAD_E_AFR: 0.0881%
gnomAD_E_AMR: 0.3839%
gnomAD_E_NFE: 0.2761%
gnomAD_E_SAS: 0.7192%
gnomAD_G_AFR: 0.0409%
gnomAD_G_AMR: 0.4244%
gnomAD_G_NFE: 0.3719%
gnomAD_G_SAS: 0.6832%
CODING_TRANSCRIPT_INTRON_VARIANT INS 16-46691958-A-ACACACACACACACACACTCT [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.657 CONTRIBUTING VARIANT
Transcripts:
ORC6:ENST00000219097.7:c.196-424_196-423insCACACACACACACACACTCT:p.(=)
Pathogenicity Data:
Best Score: 0.780591
REMM: 0.781
Frequency Data:
gnomAD_G_AFR: 0.0575%
gnomAD_G_AMR: 0.6800%
gnomAD_G_NFE: 0.4668%
gnomAD_G_SAS: 0.7740%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.000 (p=9.1E-1)

Phenotype Score: 0.252

Variant Score: 0.052

No phenotype matches to diseases with this MOI.
Variants contributing to score:
REGULATORY_REGION_VARIANT SNV 16-48057430-T-C [0/1] rs527920999
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.052 CONTRIBUTING VARIANT
Transcripts:
Pathogenicity Data:
Best Score: 0.0521786
REMM: 0.052
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 16-46694674-AC-A [0/1] rs200999001
Variant score: 0.413
Transcripts:
ORC6:ENST00000219097.7:c.450-887del:p.(=)
Pathogenicity Data:
Best Score: 0.468101
REMM: 0.468
Frequency Data:
gnomAD_G_AFR: 0.2218%
gnomAD_G_AMR: 0.6242%
gnomAD_G_EAS: 0.2962%
gnomAD_G_NFE: 0.4971%
gnomAD_G_SAS: 0.6016%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 16-46694004-C-T [1/1] rs39710
Variant score: 0.295
Transcripts:
ORC6:ENST00000219097.7:c.449+822C>T:p.(=)
Pathogenicity Data:
Best Score: 0.294891
REMM: 0.295
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 16-46693850-T-TA [1/1] rs58983698
Variant score: 0.286
Transcripts:
ORC6:ENST00000219097.7:c.449+668_449+669insA:p.(=)
Pathogenicity Data:
Best Score: 0.285714
REMM: 0.286
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 16-46693879-T-A [1|1] rs36315
Variant score: 0.285
Transcripts:
ORC6:ENST00000219097.7:c.449+697T>A:p.(=)
Pathogenicity Data:
Best Score: 0.28453
REMM: 0.285
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 16-46694371-C-T [1/1] rs40161
Variant score: 0.225
Transcripts:
ORC6:ENST00000219097.7:c.449+1189C>T:p.(=)
Pathogenicity Data:
Best Score: 0.22487
REMM: 0.225
Frequency Data:
No frequency data
REGULATORY_REGION_VARIANT SNV 16-46758007-C-T [0/1] rs113682715
Variant score: 0.008
Transcripts:
Pathogenicity Data:
Best Score: 0.00884603
REMM: 0.009
Frequency Data:
UK10K: 0.3042%
gnomAD_G_AFR: 0.0385%
gnomAD_G_AMR: 0.4252%
gnomAD_G_NFE: 0.3750%
gnomAD_G_SAS: 0.6661%

COL11A2

Exomiser Score: 0.300 (p=1.6E-1)

Phenotype Score: 0.523

Variant Score: 0.763

Phenotype matches:
Phenotypic similarity 0.523 to Fibrochondrogenesis 2 associated with COL11A2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0005257, Thoracic hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0005257, Thoracic hypoplasia
Phenotypic similarity 0.326 to mouse mutant involving COL11A2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000438, abnormal cranium morphology
HP:0006625, Multifocal breast carcinoma - MP:0000438, abnormal cranium morphology
Phenotypic similarity 0.291 to zebrafish mutant involving COL11A2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0000137, perichordal connective tissue morphology, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0000137, perichordal connective tissue morphology, abnormal
Proximity score 0.507 in interactome to SOX6 and phenotypic similarity 0.643 to Tolchin-Le Caignec syndrome associated with SOX6.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Proximity score 0.507 in interactome to SOX6 and phenotypic similarity 0.352 to mouse mutant of SOX6.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000157, abnormal sternum morphology
HP:0006625, Multifocal breast carcinoma - MP:0000157, abnormal sternum morphology
Proximity score 0.507 in interactome to SOX6 and phenotypic similarity 0.456 to fish mutant of SOX6.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0012232, vertebral column curved, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0012232, vertebral column curved, abnormal
Known diseases:
OMIM:184840 Otospondylomegaepiphyseal dysplasia, autosomal dominant - autosomal dominant
OMIM:215150 Otospondylomegaepiphyseal dysplasia, autosomal recessive - autosomal recessive
OMIM:601868 Deafness, autosomal dominant 13 - autosomal dominant
OMIM:609706 Deafness, autosomal recessive 53 - autosomal recessive
OMIM:614524 Fibrochondrogenesis 2 - autosomal dominant/recessive
ORPHA:1427 Otospondylomegaepiphyseal dysplasia - autosomal recessive
ORPHA:166100 Autosomal dominant otospondylomegaepiphyseal dysplasia - autosomal dominant
ORPHA:2021 Fibrochondrogenesis - autosomal dominant/recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.300 (p=1.6E-1)

Phenotype Score: 0.523

Variant Score: 0.763

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.523 to OMIM:614524 Fibrochondrogenesis 2
Phenotypic similarity 0.492 to ORPHA:2021 Fibrochondrogenesis
Variants contributing to score:
DOWNSTREAM_GENE_VARIANT SNV 6-33158144-T-C [1/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.763 CONTRIBUTING VARIANT
Transcripts:
COL11A2:ENST00000341947.7::
Pathogenicity Data:
Best Score: 0.762772
REMM: 0.763
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.000 (p=8.0E-1)

Phenotype Score: 0.523

Variant Score: 0.024

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.523 to OMIM:614524 Fibrochondrogenesis 2
Phenotypic similarity 0.492 to ORPHA:2021 Fibrochondrogenesis
Phenotypic similarity 0.463 to ORPHA:166100 Autosomal dominant otospondylomegaepiphyseal dysplasia
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-33166699-G-A [0/1] rs375023453
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.024 CONTRIBUTING VARIANT
Transcripts:
COL11A2:ENST00000341947.7:c.4338+21C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0239218
REMM: 0.024
Frequency Data:
gnomAD_E_AFR: 0.0627%
gnomAD_E_AMR: 0.0045%
gnomAD_E_NFE: 0.0101%
gnomAD_E_SAS: 0.0035%
gnomAD_G_AFR: 0.0798%
gnomAD_G_AMR: 0.0131%
gnomAD_G_NFE: 0.0118%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-33178983-C-G [0/1] rs182657680
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:2, LB:7, B:1)
Variant score: 0.641
Transcripts:
COL11A2:ENST00000341947.7:c.1612-10G>C:p.(=)
Pathogenicity Data:
Best Score: 0.666144
REMM: 0.666
Frequency Data:
UK10K: 0.1058%
gnomAD_E_AFR: 0.0060%
gnomAD_E_AMR: 0.0335%
gnomAD_E_NFE: 0.1263%
gnomAD_E_SAS: 0.1623%
gnomAD_G_AFR: 0.0096%
gnomAD_G_AMR: 0.0262%
gnomAD_G_EAS: 0.0388%
gnomAD_G_NFE: 0.1368%
gnomAD_G_SAS: 0.2489%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-33172883-C-T [0/1] rs552383229
Variant score: 0.057
Transcripts:
COL11A2:ENST00000341947.7:c.2790+177G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0589329
REMM: 0.059
Frequency Data:
UK10K: 0.1058%
gnomAD_G_AFR: 0.0193%
gnomAD_G_AMR: 0.0458%
gnomAD_G_EAS: 0.1354%
gnomAD_G_NFE: 0.1441%
gnomAD_G_SAS: 0.2489%

FLNB

Exomiser Score: 0.298 (p=1.6E-1)

Phenotype Score: 0.453

Variant Score: 0.841

Phenotype matches:
Phenotypic similarity 0.545 to Atelosteogenesis type I associated with FLNB.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0005257, Thoracic hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0005257, Thoracic hypoplasia
Phenotypic similarity 0.373 to mouse mutant involving FLNB.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0004624, abnormal thoracic cage morphology
HP:0006625, Multifocal breast carcinoma - MP:0004624, abnormal thoracic cage morphology
Known diseases:
OMIM:108720 Atelosteogenesis, type I - autosomal dominant
OMIM:108721 Atelosteogenesis, type III - autosomal dominant
OMIM:112310 Boomerang dysplasia - autosomal dominant
OMIM:150250 Larsen syndrome - autosomal dominant
OMIM:272460 Spondylocarpotarsal synostosis syndrome - autosomal recessive
ORPHA:1190 Atelosteogenesis type I - autosomal dominant
ORPHA:1263 Boomerang dysplasia - autosomal dominant
ORPHA:503 Larsen syndrome - autosomal dominant
ORPHA:56305 Atelosteogenesis type III - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.298 (p=1.6E-1)

Phenotype Score: 0.453

Variant Score: 0.841

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.453 to OMIM:272460 Spondylocarpotarsal synostosis syndrome
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-58131983-T-C [0/1] rs142631042
Exomiser ACMG: LIKELY_BENIGN [BP6_Strong]
ClinVar: LIKELY_BENIGN (CRITERIA_PROVIDED_MULTIPLE_SUBMITTERS_NO_CONFLICTS)
Variant score: 0.953 CONTRIBUTING VARIANT
Transcripts:
FLNB:ENST00000295956.9:c.4391-825T>C:p.(=)
Pathogenicity Data:
Best Score: 0.981995
REMM: 0.982
Frequency Data:
UK10K: 0.0132%
gnomAD_E_AFR: 0.0095%
gnomAD_E_AMR: 0.0756%
gnomAD_E_NFE: 0.0485%
gnomAD_E_SAS: 0.0416%
gnomAD_G_AFR: 0.0120%
gnomAD_G_AMR: 0.1960%
gnomAD_G_NFE: 0.0691%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-58141796-T-C [0/1] rs371398363
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.728 CONTRIBUTING VARIANT
Transcripts:
FLNB:ENST00000295956.9:c.5110-62T>C:p.(=)
Pathogenicity Data:
Best Score: 0.737037
REMM: 0.737
Frequency Data:
UK10K: 0.0397%
gnomAD_E_AFR: 0.0235%
gnomAD_E_AMR: 0.0854%
gnomAD_E_NFE: 0.0476%
gnomAD_E_SAS: 0.0863%
gnomAD_G_AFR: 0.0072%
gnomAD_G_AMR: 0.0653%
gnomAD_G_NFE: 0.0823%
gnomAD_G_SAS: 0.0621%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.282 (p=1.6E-1)

Phenotype Score: 0.545

Variant Score: 0.728

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.545 to ORPHA:1190 Atelosteogenesis type I
Phenotypic similarity 0.535 to ORPHA:56305 Atelosteogenesis type III
Phenotypic similarity 0.524 to ORPHA:1263 Boomerang dysplasia
Phenotypic similarity 0.510 to OMIM:108720 Atelosteogenesis, type I
Phenotypic similarity 0.463 to OMIM:150250 Larsen syndrome
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-58141796-T-C [0/1] rs371398363
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.728 CONTRIBUTING VARIANT
Transcripts:
FLNB:ENST00000295956.9:c.5110-62T>C:p.(=)
Pathogenicity Data:
Best Score: 0.737037
REMM: 0.737
Frequency Data:
UK10K: 0.0397%
gnomAD_E_AFR: 0.0235%
gnomAD_E_AMR: 0.0854%
gnomAD_E_NFE: 0.0476%
gnomAD_E_SAS: 0.0863%
gnomAD_G_AFR: 0.0072%
gnomAD_G_AMR: 0.0653%
gnomAD_G_NFE: 0.0823%
gnomAD_G_SAS: 0.0621%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-58062000-A-G [0/1] rs181059676
Variant score: 0.696
Transcripts:
FLNB:ENST00000295956.9:c.293-15046A>G:p.(=)
Pathogenicity Data:
Best Score: 0.702702
REMM: 0.703
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AFR: 0.0097%
gnomAD_G_AMR: 0.0591%
gnomAD_G_NFE: 0.0692%
gnomAD_G_SAS: 0.0418%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-58026815-G-C [0/1] rs144255161
Variant score: 0.678
Transcripts:
FLNB:ENST00000295956.9:c.292+17959G>C:p.(=)
Pathogenicity Data:
Best Score: 0.701179
REMM: 0.701
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AFR: 0.0072%
gnomAD_G_AMR: 0.2158%
gnomAD_G_NFE: 0.0617%
gnomAD_G_SAS: 0.0207%
UPSTREAM_GENE_VARIANT SNV 3-58004302-G-C [0/1] rs180926109
Variant score: 0.467
Transcripts:
FLNB:ENST00000295956.9::
Pathogenicity Data:
Best Score: 0.484476
REMM: 0.484
Frequency Data:
gnomAD_G_AFR: 0.0133%
gnomAD_G_AMR: 0.2371%
gnomAD_G_NFE: 0.0693%
gnomAD_G_SAS: 0.0231%
INTERGENIC_VARIANT SNV 3-57990351-G-T [0/1]
Variant score: 0.449
Transcripts:
FLNB:ENST00000295956.9::
Pathogenicity Data:
Best Score: 0.449352
REMM: 0.449
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 3-58188246-G-A [0/1] rs147275941
Variant score: 0.399
Transcripts:
FLNB:ENST00000295956.9::
Pathogenicity Data:
Best Score: 0.719149
REMM: 0.719
Frequency Data:
UK10K: 1.2298%
gnomAD_G_AFR: 0.1926%
gnomAD_G_AMR: 0.9741%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.2531%
gnomAD_G_SAS: 1.4559%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 3-58133437-GAAAA-G [0/1]
Variant score: 0.394
Transcripts:
FLNB:ENST00000295956.9:c.4514+507_4514+510del:p.(=)
Pathogenicity Data:
Best Score: 0.394214
REMM: 0.394
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 3-58073149-C-CTATTTATTTATTTATT [0/1] rs55987295
Variant score: 0.313
Transcripts:
FLNB:ENST00000295956.9:c.293-3897_293-3896insTATTTATTTATTTATT:p.(=)
Pathogenicity Data:
Best Score: 0.313166
REMM: 0.313
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 3-58136746-C-CTTTTT [0/1] rs57053256
Variant score: 0.312
Transcripts:
FLNB:ENST00000295956.9:c.4861+578_4861+579insTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.312003
REMM: 0.312
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 3-58177508-G-A [0/1] rs6807500
Variant score: 0.284
Transcripts:
FLNB:ENST00000295956.9::
Pathogenicity Data:
Best Score: 0.541583
REMM: 0.542
Frequency Data:
UK10K: 1.2034%
gnomAD_G_AFR: 0.1864%
gnomAD_G_AMR: 0.9400%
gnomAD_G_EAS: 0.0195%
gnomAD_G_NFE: 1.2155%
gnomAD_G_SAS: 1.5075%
UPSTREAM_GENE_VARIANT DEL 3-58007317-GTTTTT-G [1/1] rs56890071
Variant score: 0.264
Transcripts:
FLNB:ENST00000295956.9::
Pathogenicity Data:
Best Score: 0.264469
REMM: 0.264
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 3-58018327-CT-C [1/1] rs60851192
Variant score: 0.250
Transcripts:
FLNB:ENST00000295956.9:c.292+9472del:p.(=)
Pathogenicity Data:
Best Score: 0.249987
REMM: 0.250
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 3-58045999-CA-C [1/1] rs34327981
Variant score: 0.250
Transcripts:
FLNB:ENST00000295956.9:c.293-31046del:p.(=)
Pathogenicity Data:
Best Score: 0.249829
REMM: 0.250
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT DEL 3-58007312-TTTCTG-T [0/1] rs2097090872
Variant score: 0.234
Transcripts:
FLNB:ENST00000295956.9::
Pathogenicity Data:
Best Score: 0.233772
REMM: 0.234
Frequency Data:
gnomAD_G_NFE: 0.0031%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-58018962-C-A [0/1] rs1175656223
Variant score: 0.201
Transcripts:
FLNB:ENST00000295956.9:c.292+10106C>A:p.(=)
Pathogenicity Data:
Best Score: 0.20139
REMM: 0.201
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 3-58106352-C-CTATATATATATATATATA [0/1] rs10540627
Variant score: 0.143
Transcripts:
FLNB:ENST00000295956.9:c.1748-328_1748-327insTATATATATATATATATA:p.(=)
Pathogenicity Data:
Best Score: 0.188777
REMM: 0.189
Frequency Data:
gnomAD_G_AFR: 0.7502%
gnomAD_G_AMR: 0.9081%
gnomAD_G_NFE: 0.8067%
gnomAD_G_SAS: 1.0307%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 3-58060769-CAAA-C [0/1]
Variant score: 0.131
Transcripts:
FLNB:ENST00000295956.9:c.293-16276_293-16274del:p.(=)
Pathogenicity Data:
Best Score: 0.130724
REMM: 0.131
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 3-58060769-CAAAA-C [0/1]
Variant score: 0.131
Transcripts:
FLNB:ENST00000295956.9:c.293-16276_293-16273del:p.(=)
Pathogenicity Data:
Best Score: 0.130724
REMM: 0.131
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 3-58071274-CT-C [0/1] rs57488190
Variant score: 0.047
Transcripts:
FLNB:ENST00000295956.9:c.293-5771del:p.(=)
Pathogenicity Data:
Best Score: 0.0465151
REMM: 0.047
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-58170090-G-A [0/1] rs765828394
Variant score: 0.013
Transcripts:
FLNB:ENST00000295956.9:c.7621+297G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0130302
REMM: 0.013
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AMR: 0.0131%
gnomAD_G_EAS: 0.0385%
gnomAD_G_NFE: 0.0059%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-58053561-A-G [0/1] rs181765594
Variant score: 0.004
Transcripts:
FLNB:ENST00000295956.9:c.293-23485A>G:p.(=)
Pathogenicity Data:
Best Score: 0.00354206
REMM: 0.004
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AFR: 0.0120%
gnomAD_G_AMR: 0.0327%
gnomAD_G_NFE: 0.0632%
gnomAD_G_SAS: 0.0208%
UPSTREAM_GENE_VARIANT SNV 3-58003637-G-T [0/1] rs551065577
Variant score: 0.002
Transcripts:
FLNB:ENST00000295956.9::
Pathogenicity Data:
Best Score: 0.00170159
REMM: 0.002
Frequency Data:
gnomAD_G_AFR: 0.0289%
gnomAD_G_AMR: 0.0131%
gnomAD_G_NFE: 0.0059%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-58130496-G-C [0/1]
Variant score: 0.001
Transcripts:
FLNB:ENST00000295956.9:c.4223-245G>C:p.(=)
Pathogenicity Data:
Best Score: 0.001
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 3-58069232-CT-C [1/1] rs59689498
Variant score: 0.001
Transcripts:
FLNB:ENST00000295956.9:c.293-7813del:p.(=)
Pathogenicity Data:
Best Score: 8.66667E-4
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-58046455-G-T [0/1] rs1025974945
Variant score: 0.000
Transcripts:
FLNB:ENST00000295956.9:c.293-30591G>T:p.(=)
Pathogenicity Data:
Best Score: 2.5E-4
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.1376%
gnomAD_G_AMR: 0.9551%
gnomAD_G_EAS: 0.0202%
gnomAD_G_NFE: 1.0005%
gnomAD_G_SAS: 1.0412%

GRIP1

Exomiser Score: 0.277 (p=1.6E-1)

Phenotype Score: 0.569

Variant Score: 0.699

Phenotype matches:
Phenotypic similarity 0.569 to Fraser syndrome associated with GRIP1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0006610, Wide intermamillary distance
HP:0006625, Multifocal breast carcinoma - HP:0006610, Wide intermamillary distance
Proximity score 0.502 in interactome to OPCML and phenotypic similarity 0.998 to Ovarian cancer, somatic associated with OPCML.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Known diseases:
OMIM:617667 Fraser syndrome 3 - autosomal recessive
ORPHA:2052 Fraser syndrome - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.277 (p=1.6E-1)

Phenotype Score: 0.569

Variant Score: 0.699

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.569 to ORPHA:2052 Fraser syndrome
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66625395-C-G [0/1] rs1442688208
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.771 CONTRIBUTING VARIANT
Transcripts:
GRIP1:ENST00000359742.9:c.56-28468G>C:p.(=)
Pathogenicity Data:
Best Score: 0.771426
REMM: 0.771
Frequency Data:
gnomAD_G_NFE: 0.0044%
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-66617085-T-TGTGTGTG [0/1] rs370300223
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.627 CONTRIBUTING VARIANT
Transcripts:
GRIP1:ENST00000359742.9:c.56-20159_56-20158insCACACAC:p.(=)
Pathogenicity Data:
Best Score: 0.626634
REMM: 0.627
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.027 (p=3.8E-1)

Phenotype Score: 0.251

Variant Score: 0.771

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66625395-C-G [0/1] rs1442688208
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.771 CONTRIBUTING VARIANT
Transcripts:
GRIP1:ENST00000359742.9:c.56-28468G>C:p.(=)
Pathogenicity Data:
Best Score: 0.771426
REMM: 0.771
Frequency Data:
gnomAD_G_NFE: 0.0044%
Other passed variants:
MISSENSE_VARIANT SNV 12-66541927-C-T [0/1] rs199768740
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:4, LB:2)
Variant score: 0.585
Transcripts:
GRIP1:ENST00000359742.9:c.160G>A:p.(Val54Ile)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.0793%
gnomAD_E_AFR: 0.0269%
gnomAD_E_AMR: 0.1744%
gnomAD_E_NFE: 0.0727%
gnomAD_E_SAS: 0.1449%
gnomAD_G_AFR: 0.0217%
gnomAD_G_AMR: 0.1634%
gnomAD_G_NFE: 0.0941%
gnomAD_G_SAS: 0.0831%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66388453-A-G [0/1]
Variant score: 0.562
Transcripts:
GRIP1:ENST00000359742.9:c.2464+3855T>C:p.(=)
Pathogenicity Data:
Best Score: 0.562291
REMM: 0.562
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66535506-T-C [0/1] rs974417192
Variant score: 0.510
Transcripts:
GRIP1:ENST00000359742.9:c.418+3572A>G:p.(=)
Pathogenicity Data:
Best Score: 0.510294
REMM: 0.510
Frequency Data:
gnomAD_G_AFR: 0.0024%
gnomAD_G_NFE: 0.0103%
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-66617085-T-TTGTGTGTGTGTGTG [0/1] rs71436017
Variant score: 0.477
Transcripts:
GRIP1:ENST00000359742.9:c.56-20159_56-20158insCACACACACACACA:p.(=)
Pathogenicity Data:
Best Score: 0.626634
REMM: 0.627
Frequency Data:
gnomAD_G_AFR: 1.0158%
gnomAD_G_AMR: 0.3422%
gnomAD_G_EAS: 1.0164%
gnomAD_G_NFE: 0.4567%
gnomAD_G_SAS: 0.5861%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66626219-G-A [0|1] rs143933118
Variant score: 0.418
Transcripts:
GRIP1:ENST00000359742.9:c.56-29292C>T:p.(=)
Pathogenicity Data:
Best Score: 0.56782
REMM: 0.568
Frequency Data:
UK10K: 0.6876%
gnomAD_G_AFR: 0.1665%
gnomAD_G_AMR: 0.4065%
gnomAD_G_NFE: 1.0807%
gnomAD_G_SAS: 0.7923%
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-66602847-G-GTTT [0/1] rs2064337240
Variant score: 0.350
Transcripts:
GRIP1:ENST00000359742.9:c.56-5921_56-5920insAAA:p.(=)
Pathogenicity Data:
Best Score: 0.349688
REMM: 0.350
Frequency Data:
gnomAD_G_NFE: 0.0030%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-66539545-CTT-C [0/1] rs35373698
Variant score: 0.340
Transcripts:
GRIP1:ENST00000359742.9:c.273-324_273-323del:p.(=)
Pathogenicity Data:
Best Score: 0.339703
REMM: 0.340
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-66451383-GTTTTTTTTT-G [0/1] rs1169331519
Variant score: 0.336
Transcripts:
GRIP1:ENST00000359742.9:c.1354+4017_1354+4025del:p.(=)
Pathogenicity Data:
Best Score: 0.360733
REMM: 0.361
Frequency Data:
gnomAD_G_AFR: 0.4096%
gnomAD_G_AMR: 0.0318%
gnomAD_G_NFE: 0.0460%
gnomAD_G_SAS: 0.0786%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-66450303-CAA-C [0/1]
Variant score: 0.326
Transcripts:
GRIP1:ENST00000359742.9:c.1355-4797_1355-4796del:p.(=)
Pathogenicity Data:
Best Score: 0.325504
REMM: 0.326
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-66531342-T-TAC [1/1]
Variant score: 0.176
Transcripts:
GRIP1:ENST00000359742.9:c.419-1429_419-1428insGT:p.(=)
Pathogenicity Data:
Best Score: 0.175986
REMM: 0.176
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-66401609-T-TATATATATATATACACAC [0/1] rs1169241331
Variant score: 0.124
Transcripts:
GRIP1:ENST00000359742.9:c.1984+4673_1984+4674insGTGTGTATATATATATAT:p.(=)
Pathogenicity Data:
Best Score: 0.131665
REMM: 0.132
Frequency Data:
gnomAD_G_AFR: 0.2052%
gnomAD_G_AMR: 0.2391%
gnomAD_G_EAS: 0.3567%
gnomAD_G_NFE: 0.1257%
gnomAD_G_SAS: 0.2584%
SYNONYMOUS_VARIANT SNV 12-66392489-C-T [0/1] rs200863167
ClinVar: BENIGN_OR_LIKELY_BENIGN (CRITERIA_PROVIDED_MULTIPLE_SUBMITTERS_NO_CONFLICTS)
Variant score: 0.096
Transcripts:
GRIP1:ENST00000359742.9:c.2283G>A:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.1455%
gnomAD_E_AFR: 0.0269%
gnomAD_E_AMR: 0.2079%
gnomAD_E_NFE: 0.1128%
gnomAD_E_SAS: 0.2470%
gnomAD_G_AFR: 0.0241%
gnomAD_G_AMR: 0.2159%
gnomAD_G_NFE: 0.1397%
gnomAD_G_SAS: 0.2497%
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-66477809-G-GA [0/1] rs199708413
Variant score: 0.062
Transcripts:
GRIP1:ENST00000359742.9:c.725-12388_725-12387insT:p.(=)
Pathogenicity Data:
Best Score: 0.0617778
REMM: 0.062
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66584175-G-A [0/1] rs144181791
Variant score: 0.059
Transcripts:
GRIP1:ENST00000359742.9:c.136+12672C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0594266
REMM: 0.059
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-66531247-AAAAAAATATATATATATATATATATATATATATAT-A [0/1] rs1241432474
Variant score: 0.058
Transcripts:
GRIP1:ENST00000359742.9:c.419-1368_419-1334del:p.(=)
Pathogenicity Data:
Best Score: 0.149387
REMM: 0.149
Frequency Data:
gnomAD_G_AFR: 0.1147%
gnomAD_G_AMR: 0.0450%
gnomAD_G_EAS: 0.5387%
gnomAD_G_NFE: 0.0544%
gnomAD_G_SAS: 1.7112%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66584209-G-A [0|1] rs201963499
Variant score: 0.050
Transcripts:
GRIP1:ENST00000359742.9:c.136+12638C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0502036
REMM: 0.050
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66583834-G-T [0|1] rs796642457
Variant score: 0.040
Transcripts:
GRIP1:ENST00000359742.9:c.136+13013C>A:p.(=)
Pathogenicity Data:
Best Score: 0.0402476
REMM: 0.040
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66583833-T-G [0|1] rs796451506
Variant score: 0.033
Transcripts:
GRIP1:ENST00000359742.9:c.136+13014A>C:p.(=)
Pathogenicity Data:
Best Score: 0.0332476
REMM: 0.033
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66585270-C-A [0/1] rs7966886
Variant score: 0.032
Transcripts:
GRIP1:ENST00000359742.9:c.136+11577G>T:p.(=)
Pathogenicity Data:
Best Score: 0.0323444
REMM: 0.032
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66425879-G-A [0/1] rs184402786
Variant score: 0.031
Transcripts:
GRIP1:ENST00000359742.9:c.1769-5090C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0957278
REMM: 0.096
Frequency Data:
gnomAD_G_AFR: 0.2696%
gnomAD_G_AMR: 1.1265%
gnomAD_G_EAS: 0.0773%
gnomAD_G_NFE: 1.7968%
gnomAD_G_SAS: 0.8299%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66661479-A-G [0|1]
Variant score: 0.028
Transcripts:
GRIP1:ENST00000359742.9:c.55+17371T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0275115
REMM: 0.028
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66583711-C-T [0|1] rs75167787
Variant score: 0.020
Transcripts:
GRIP1:ENST00000359742.9:c.136+13136G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0210786
REMM: 0.021
Frequency Data:
gnomAD_G_AFR: 0.1365%
gnomAD_G_AMR: 0.0994%
gnomAD_G_EAS: 0.2587%
gnomAD_G_NFE: 0.0932%
gnomAD_G_SAS: 0.2044%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66523358-G-C [1/1] rs113129124
Variant score: 0.020
Transcripts:
GRIP1:ENST00000359742.9:c.503-5382C>G:p.(=)
Pathogenicity Data:
Best Score: 0.019998
REMM: 0.020
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66585307-A-G [0/1] rs7966793
Variant score: 0.019
Transcripts:
GRIP1:ENST00000359742.9:c.136+11540T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0191405
REMM: 0.019
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66583862-G-C [0/1] rs113880639
Variant score: 0.018
Transcripts:
GRIP1:ENST00000359742.9:c.136+12985C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0182921
REMM: 0.018
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66583807-G-A [0/1] rs200241445
Variant score: 0.014
Transcripts:
GRIP1:ENST00000359742.9:c.136+13040C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0147698
REMM: 0.015
Frequency Data:
gnomAD_G_AFR: 0.2182%
gnomAD_G_AMR: 0.2617%
gnomAD_G_EAS: 0.3452%
gnomAD_G_NFE: 0.2425%
gnomAD_G_SAS: 0.2123%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66583703-G-A [0|1] rs1441780540
Variant score: 0.012
Transcripts:
GRIP1:ENST00000359742.9:c.136+13144C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0123095
REMM: 0.012
Frequency Data:
gnomAD_G_AFR: 0.1310%
gnomAD_G_AMR: 0.1409%
gnomAD_G_EAS: 0.2131%
gnomAD_G_NFE: 0.1200%
gnomAD_G_SAS: 0.3066%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66585673-G-A [0/1] rs113263229
Variant score: 0.011
Transcripts:
GRIP1:ENST00000359742.9:c.136+11174C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0113762
REMM: 0.011
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66585604-T-C [0/1] rs112485107
Variant score: 0.009
Transcripts:
GRIP1:ENST00000359742.9:c.136+11243A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0090619
REMM: 0.009
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66582286-A-C [0/1] rs12307029
Variant score: 0.008
Transcripts:
GRIP1:ENST00000359742.9:c.136+14561T>G:p.(=)
Pathogenicity Data:
Best Score: 0.00842222
REMM: 0.008
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66585560-A-C [0/1] rs112361304
Variant score: 0.008
Transcripts:
GRIP1:ENST00000359742.9:c.136+11287T>G:p.(=)
Pathogenicity Data:
Best Score: 0.00814762
REMM: 0.008
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66583680-G-A [0/1] rs71452314
Variant score: 0.008
Transcripts:
GRIP1:ENST00000359742.9:c.136+13167C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00891429
REMM: 0.009
Frequency Data:
gnomAD_G_AFR: 0.4680%
gnomAD_G_AMR: 0.5829%
gnomAD_G_EAS: 0.7178%
gnomAD_G_NFE: 0.4147%
gnomAD_G_SAS: 0.5550%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66583999-C-G [0/1] rs111581354
Variant score: 0.006
Transcripts:
GRIP1:ENST00000359742.9:c.136+12848G>C:p.(=)
Pathogenicity Data:
Best Score: 0.00570278
REMM: 0.006
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66583888-T-C [0/1] rs200847633
Variant score: 0.004
Transcripts:
GRIP1:ENST00000359742.9:c.136+12959A>G:p.(=)
Pathogenicity Data:
Best Score: 0.00383889
REMM: 0.004
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66584213-T-A [0|1] rs74693613
Variant score: 0.002
Transcripts:
GRIP1:ENST00000359742.9:c.136+12634A>T:p.(=)
Pathogenicity Data:
Best Score: 0.00233333
REMM: 0.002
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66617700-C-A [0/1] rs11176326
Variant score: 0.001
Transcripts:
GRIP1:ENST00000359742.9:c.56-20773G>T:p.(=)
Pathogenicity Data:
Best Score: 0.0013
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-66446094-G-GCCGCCCCCCCACC [0/1] rs140993793
Variant score: 0.001
Transcripts:
GRIP1:ENST00000359742.9:c.1355-587_1355-586insGGTGGGGGGGCGG:p.(=)
Pathogenicity Data:
Best Score: 0.00112778
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66405899-C-T [0/1] rs184073587
Variant score: 0.000
Transcripts:
GRIP1:ENST00000359742.9:c.1984+384G>A:p.(=)
Pathogenicity Data:
Best Score: 4.78968E-4
REMM: 0.000
Frequency Data:
UK10K: 0.1190%
gnomAD_G_AFR: 0.0361%
gnomAD_G_AMR: 0.2095%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.1456%
gnomAD_G_SAS: 0.2281%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66507210-G-A [0/1] rs867745715
Variant score: 0.000
Transcripts:
GRIP1:ENST00000359742.9:c.724+8409C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0289%
gnomAD_G_AMR: 0.1896%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 0.1059%
gnomAD_G_SAS: 0.1662%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66531302-T-C [0|1]
Variant score: 0.000
Transcripts:
GRIP1:ENST00000359742.9:c.419-1388A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-66539545-CT-C [0/1] rs35373698
Variant score: 0.000
Transcripts:
GRIP1:ENST00000359742.9:c.273-323del:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-66578231-G-GTTTTTTTTTTTTTTTT [0/1] rs1462512737
Variant score: 0.000
Transcripts:
GRIP1:ENST00000359742.9:c.136+18615_136+18616insAAAAAAAAAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0343%
gnomAD_G_AMR: 0.2155%
gnomAD_G_NFE: 0.2285%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66578232-G-T [0/1] rs866262545
Variant score: 0.000
Transcripts:
GRIP1:ENST00000359742.9:c.136+18615C>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-66606792-C-T [0/1] rs2064551114
Variant score: 0.000
Transcripts:
GRIP1:ENST00000359742.9:c.56-9865G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_NFE: 0.0015%

ACACA

Exomiser Score: 0.274 (p=1.7E-1)

Phenotype Score: 0.504

Variant Score: 0.770

Phenotype matches:
Proximity score 0.504 in interactome to RAD51C and phenotypic similarity 0.998 to Hereditary breast and/or ovarian cancer syndrome associated with RAD51C.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Known diseases:
OMIM:613933 Acetyl-CoA carboxylase deficiency - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.274 (p=1.7E-1)

Phenotype Score: 0.504

Variant Score: 0.770

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-37317806-A-G [0/1] rs750225710
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.883 CONTRIBUTING VARIANT
Transcripts:
ACACA:ENST00000616317.5:c.338+12367T>C:p.(=)
Pathogenicity Data:
Best Score: 0.882577
REMM: 0.883
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-37353637-T-TAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.658 CONTRIBUTING VARIANT
Transcripts:
ACACA:ENST00000616317.5:c.39-13788_39-13787insTT:p.(=)
Pathogenicity Data:
Best Score: 0.657551
REMM: 0.658
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.072 (p=2.9E-1)

Phenotype Score: 0.252

Variant Score: 0.883

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-37317806-A-G [0/1] rs750225710
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.883 CONTRIBUTING VARIANT
Transcripts:
ACACA:ENST00000616317.5:c.338+12367T>C:p.(=)
Pathogenicity Data:
Best Score: 0.882577
REMM: 0.883
Frequency Data:
No frequency data
Other passed variants:
MISSENSE_VARIANT SNV 17-37283366-T-C [0/1] rs779622678
Variant score: 0.600
Transcripts:
ACACA:ENST00000616317.5:c.511A>G:p.(Met171Val)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_NFE: 0.0001%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-37177095-C-T [0/1] rs116844954
Variant score: 0.402
Transcripts:
ACACA:ENST00000616317.5:c.5079+2165G>A:p.(=)
Pathogenicity Data:
Best Score: 0.722592
REMM: 0.723
Frequency Data:
UK10K: 1.3753%
gnomAD_G_AFR: 0.2360%
gnomAD_G_AMR: 0.6344%
gnomAD_G_NFE: 1.4529%
gnomAD_G_SAS: 0.4983%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-37238106-C-G [0/1] rs1202150213
Variant score: 0.294
Transcripts:
ACACA:ENST00000616317.5:c.3121+2370G>C:p.(=)
Pathogenicity Data:
Best Score: 0.29446
REMM: 0.294
Frequency Data:
gnomAD_G_NFE: 0.0015%
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-37348948-C-CA [0/1]
Variant score: 0.290
Transcripts:
ACACA:ENST00000616317.5:c.39-9099_39-9098insT:p.(=)
Pathogenicity Data:
Best Score: 0.290413
REMM: 0.290
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 17-37305904-GT-G [0/1] rs200591761
Variant score: 0.229
Transcripts:
ACACA:ENST00000616317.5:c.339-20935del:p.(=)
Pathogenicity Data:
Best Score: 0.229296
REMM: 0.229
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-37383988-G-A [0/1] rs774715232
Variant score: 0.220
Transcripts:
ACACA:ENST00000616317.5:c.38+22274C>T:p.(=)
Pathogenicity Data:
Best Score: 0.221352
REMM: 0.221
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AMR: 0.0590%
gnomAD_G_NFE: 0.0074%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 17-37174020-ATTT-A [0/1] rs71159693
Variant score: 0.164
Transcripts:
ACACA:ENST00000616317.5:c.5079+5237_5079+5239del:p.(=)
Pathogenicity Data:
Best Score: 0.171043
REMM: 0.171
Frequency Data:
gnomAD_G_AFR: 0.0511%
gnomAD_G_AMR: 0.2519%
gnomAD_G_EAS: 0.1880%
gnomAD_G_NFE: 0.2172%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 17-37174020-ATTTTT-A [0/1] rs71159693
Variant score: 0.145
Transcripts:
ACACA:ENST00000616317.5:c.5079+5235_5079+5239del:p.(=)
Pathogenicity Data:
Best Score: 0.171043
REMM: 0.171
Frequency Data:
gnomAD_G_AFR: 0.2808%
gnomAD_G_AMR: 0.3797%
gnomAD_G_NFE: 0.7507%
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-37157531-C-CT [0/1] rs397687787
Variant score: 0.142
Transcripts:
ACACA:ENST00000616317.5:c.5350-1752_5350-1751insA:p.(=)
Pathogenicity Data:
Best Score: 0.141701
REMM: 0.142
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 17-37305903-TG-T [0/1]
Variant score: 0.137
Transcripts:
ACACA:ENST00000616317.5:c.339-20934del:p.(=)
Pathogenicity Data:
Best Score: 0.136538
REMM: 0.137
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 17-37390140-GTATATATA-G [0/1]
Variant score: 0.126
Transcripts:
ACACA:ENST00000616317.5:c.38+16114_38+16121del:p.(=)
Pathogenicity Data:
Best Score: 0.125575
REMM: 0.126
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 17-37342432-AAAAAAT-A [0/1] rs1376588666
Variant score: 0.055
Transcripts:
ACACA:ENST00000616317.5:c.39-2588_39-2583del:p.(=)
Pathogenicity Data:
Best Score: 0.0546159
REMM: 0.055
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 17-37260249-CATAT-C [1/1]
Variant score: 0.054
Transcripts:
ACACA:ENST00000616317.5:c.1330-723_1330-720del:p.(=)
Pathogenicity Data:
Best Score: 0.0539274
REMM: 0.054
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-37342438-T-A [0/1]
Variant score: 0.043
Transcripts:
ACACA:ENST00000616317.5:c.39-2588A>T:p.(=)
Pathogenicity Data:
Best Score: 0.0427738
REMM: 0.043
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 17-37390311-TATA-T [0/1]
Variant score: 0.042
Transcripts:
ACACA:ENST00000616317.5:c.38+15948_38+15950del:p.(=)
Pathogenicity Data:
Best Score: 0.0418675
REMM: 0.042
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-37390173-T-C [0|1] rs1405663681
Variant score: 0.040
Transcripts:
ACACA:ENST00000616317.5:c.38+16089A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0401024
REMM: 0.040
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-37390322-A-AAT [0/1]
Variant score: 0.037
Transcripts:
ACACA:ENST00000616317.5:c.38+15939_38+15940insAT:p.(=)
Pathogenicity Data:
Best Score: 0.0365833
REMM: 0.037
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-37398591-G-A [1/1] rs113593735
Variant score: 0.001
Transcripts:
ACACA:ENST00000616317.5:c.38+7671C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00118056
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-37398728-C-T [1|1] rs573347636
Variant score: 0.001
Transcripts:
ACACA:ENST00000616317.5:c.38+7534G>A:p.(=)
Pathogenicity Data:
Best Score: 0.001
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-37398643-A-G [1|1] rs371861336
Variant score: 0.001
Transcripts:
ACACA:ENST00000616317.5:c.38+7619T>C:p.(=)
Pathogenicity Data:
Best Score: 8.33333E-4
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-37398647-G-A [1|1] rs374995229
Variant score: 0.000
Transcripts:
ACACA:ENST00000616317.5:c.38+7615C>T:p.(=)
Pathogenicity Data:
Best Score: 3.33333E-4
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-37186910-G-A [0/1]
Variant score: 0.000
Transcripts:
ACACA:ENST00000616317.5:c.4776+1367C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-37398653-A-G [1|1] rs926093131
Variant score: 0.000
Transcripts:
ACACA:ENST00000616317.5:c.38+7609T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-37398660-C-T [1|1] rs936115170
Variant score: 0.000
Transcripts:
ACACA:ENST00000616317.5:c.38+7602G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-37398686-C-T [1/1] rs1282322784
Variant score: 0.000
Transcripts:
ACACA:ENST00000616317.5:c.38+7576G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-37398694-C-A [0/1] rs1377869290
Variant score: 0.000
Transcripts:
ACACA:ENST00000616317.5:c.38+7568G>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-37398700-T-C [1/1] rs1459196520
Variant score: 0.000
Transcripts:
ACACA:ENST00000616317.5:c.38+7562A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-37398731-C-A [1|1] rs368617487
Variant score: 0.000
Transcripts:
ACACA:ENST00000616317.5:c.38+7531G>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data

MCPH1

Exomiser Score: 0.267 (p=1.7E-1)

Phenotype Score: 0.505

Variant Score: 0.765

Phenotype matches:
Phenotypic similarity 0.319 to mouse mutant involving MCPH1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000063, decreased bone mineral density
HP:0006625, Multifocal breast carcinoma - MP:0000063, decreased bone mineral density
Proximity score 0.505 in interactome to SET and phenotypic similarity 0.643 to Intellectual developmental disorder, autosomal dominant 58 associated with SET.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Known diseases:
OMIM:251200 Microcephaly 1, primary, autosomal recessive - autosomal recessive
ORPHA:2512 Autosomal recessive primary microcephaly - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.267 (p=1.7E-1)

Phenotype Score: 0.505

Variant Score: 0.765

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-6409717-G-C [0/1] rs907585006
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.786 CONTRIBUTING VARIANT
Transcripts:
MCPH1:ENST00000344683.10:c.114+347G>C:p.(=)
Pathogenicity Data:
Best Score: 0.786566
REMM: 0.787
Frequency Data:
gnomAD_G_AMR: 0.0065%
gnomAD_G_NFE: 0.0059%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-6528499-TC-T [0/1] rs371338591
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.745 CONTRIBUTING VARIANT
Transcripts:
MCPH1:ENST00000344683.10:c.2214+28571del:p.(=)
Pathogenicity Data:
Best Score: 0.783381
REMM: 0.783
Frequency Data:
UK10K: 0.2380%
gnomAD_G_AFR: 0.0337%
gnomAD_G_AMR: 0.2156%
gnomAD_G_EAS: 0.0578%
gnomAD_G_NFE: 0.2469%
gnomAD_G_SAS: 0.3108%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.031 (p=3.6E-1)

Phenotype Score: 0.253

Variant Score: 0.786

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-6409717-G-C [0/1] rs907585006
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.786 CONTRIBUTING VARIANT
Transcripts:
MCPH1:ENST00000344683.10:c.114+347G>C:p.(=)
Pathogenicity Data:
Best Score: 0.786566
REMM: 0.787
Frequency Data:
gnomAD_G_AMR: 0.0065%
gnomAD_G_NFE: 0.0059%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-6563976-CT-C [1/1] rs11358428
Variant score: 0.724
Transcripts:
MCPH1:ENST00000344683.10:c.2215-57477del:p.(=)
Pathogenicity Data:
Best Score: 0.723641
REMM: 0.724
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-6516641-A-T [0/1] rs528033476
Variant score: 0.705
Transcripts:
MCPH1:ENST00000344683.10:c.2214+16712A>T:p.(=)
Pathogenicity Data:
Best Score: 0.722637
REMM: 0.723
Frequency Data:
gnomAD_G_AMR: 0.1176%
gnomAD_G_EAS: 0.0385%
gnomAD_G_NFE: 0.0220%
gnomAD_G_SAS: 0.1656%
DOWNSTREAM_GENE_VARIANT INS 8-6649311-T-TACAGAACAGGTGACTAAGGGTGATTAAGG [1/1] rs11270417
Variant score: 0.639
Transcripts:
MCPH1:ENST00000344683.10::
Pathogenicity Data:
Best Score: 0.639357
REMM: 0.639
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-6562552-C-CTTTTTTTTTTTTTTTT [0/1] rs55804146
Variant score: 0.621
Transcripts:
MCPH1:ENST00000344683.10:c.2215-58902_2215-58901insTTTTTTTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.621106
REMM: 0.621
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-6496922-A-G [0/1] rs530244187
Variant score: 0.619
Transcripts:
MCPH1:ENST00000344683.10:c.2137-2930A>G:p.(=)
Pathogenicity Data:
Best Score: 0.632318
REMM: 0.632
Frequency Data:
gnomAD_G_AMR: 0.0523%
gnomAD_G_EAS: 0.0386%
gnomAD_G_NFE: 0.0103%
gnomAD_G_SAS: 0.1452%
MISSENSE_VARIANT SNV 8-6499914-C-G [0/1] rs202015253
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:2, LB:1)
Variant score: 0.587
Transcripts:
MCPH1:ENST00000344683.10:c.2199C>G:p.(His733Gln)
MCPH1:ENST00000629816.3:c.*3187G>C:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 0.0060%
gnomAD_E_AMR: 0.0134%
gnomAD_E_NFE: 0.0042%
gnomAD_E_SAS: 0.0881%
gnomAD_G_AMR: 0.0523%
gnomAD_G_EAS: 0.0386%
gnomAD_G_NFE: 0.0103%
gnomAD_G_SAS: 0.1451%
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-6559230-A-AACAC [0/1] rs59299448
Variant score: 0.488
Transcripts:
MCPH1:ENST00000344683.10:c.2214+59301_2214+59302insACAC:p.(=)
Pathogenicity Data:
Best Score: 0.810215
REMM: 0.810
Frequency Data:
gnomAD_G_AFR: 1.3711%
gnomAD_G_AMR: 0.7488%
gnomAD_G_EAS: 0.5030%
gnomAD_G_NFE: 0.5208%
gnomAD_G_SAS: 0.8682%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-6530508-CA-C [1/1]
Variant score: 0.445
Transcripts:
MCPH1:ENST00000344683.10:c.2214+30580del:p.(=)
Pathogenicity Data:
Best Score: 0.444578
REMM: 0.445
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-6514466-G-T [0/1] rs866270960
Variant score: 0.431
Transcripts:
MCPH1:ENST00000344683.10:c.2214+14537G>T:p.(=)
Pathogenicity Data:
Best Score: 0.441759
REMM: 0.442
Frequency Data:
gnomAD_G_AMR: 0.0588%
gnomAD_G_EAS: 0.0387%
gnomAD_G_NFE: 0.0162%
gnomAD_G_SAS: 0.1659%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-6570476-G-A [0/1] rs147697539
Variant score: 0.375
Transcripts:
MCPH1:ENST00000344683.10:c.2215-50978G>A:p.(=)
Pathogenicity Data:
Best Score: 0.533028
REMM: 0.533
Frequency Data:
UK10K: 0.8596%
gnomAD_G_AFR: 0.2190%
gnomAD_G_AMR: 0.6281%
gnomAD_G_EAS: 0.0963%
gnomAD_G_NFE: 1.0382%
gnomAD_G_SAS: 1.1618%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-6566907-C-T [0/1] rs933251057
Variant score: 0.367
Transcripts:
MCPH1:ENST00000344683.10:c.2215-54547C>T:p.(=)
Pathogenicity Data:
Best Score: 0.368373
REMM: 0.368
Frequency Data:
gnomAD_G_AFR: 0.0234%
gnomAD_G_NFE: 0.0030%
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-6576498-T-TCCCTTCCCCTTC [1/1] rs143775843
Variant score: 0.299
Transcripts:
MCPH1:ENST00000344683.10:c.2215-44956_2215-44955insCCCTTCCCCTTC:p.(=)
Pathogenicity Data:
Best Score: 0.29927
REMM: 0.299
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-6466127-GGATTTT-G [0/1] rs747648729
Variant score: 0.276
Transcripts:
MCPH1:ENST00000344683.10:c.1935+10876_1935+10881del:p.(=)
Pathogenicity Data:
Best Score: 0.276062
REMM: 0.276
Frequency Data:
No frequency data
INTERGENIC_VARIANT INS 8-6667659-A-AAGGAAGGG [1/1] rs71214953
Variant score: 0.236
Transcripts:
MCPH1:ENST00000344683.10::
Pathogenicity Data:
Best Score: 0.236151
REMM: 0.236
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-6505181-T-C [0/1] rs866562353
Variant score: 0.229
Transcripts:
MCPH1:ENST00000344683.10:c.2214+5252T>C:p.(=)
Pathogenicity Data:
Best Score: 0.23151
REMM: 0.232
Frequency Data:
gnomAD_G_AMR: 0.0143%
gnomAD_G_EAS: 0.0199%
gnomAD_G_NFE: 0.0045%
gnomAD_G_SAS: 0.0637%
INTERGENIC_VARIANT SNV 8-6655659-C-T [1|1] rs11786695
Variant score: 0.196
Transcripts:
MCPH1:ENST00000344683.10::
Pathogenicity Data:
Best Score: 0.196085
REMM: 0.196
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT DEL 8-6404162-CAAA-C [1/1]
Variant score: 0.192
Transcripts:
MCPH1:ENST00000344683.10::
Pathogenicity Data:
Best Score: 0.192281
REMM: 0.192
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT DEL 8-6401844-CTTTTT-C [0/1] rs10616106
Variant score: 0.177
Transcripts:
MCPH1:ENST00000344683.10::
Pathogenicity Data:
Best Score: 0.17696
REMM: 0.177
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-6505397-A-ATG [1/1]
Variant score: 0.147
Transcripts:
MCPH1:ENST00000344683.10:c.2214+5468_2214+5469insTG:p.(=)
Pathogenicity Data:
Best Score: 0.147122
REMM: 0.147
Frequency Data:
No frequency data
REGULATORY_REGION_VARIANT INS 8-6312807-T-TAAAAAAAA [0/1] rs57213390
Variant score: 0.147
Transcripts:
MCPH1:ENST00000344683.10::
MCPH1:ENST00000635120.2::
Pathogenicity Data:
Best Score: 0.146915
REMM: 0.147
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-6473320-C-CT [0/1] rs56077837
Variant score: 0.138
Transcripts:
MCPH1:ENST00000344683.10:c.1936-4274_1936-4273insT:p.(=)
Pathogenicity Data:
Best Score: 0.138149
REMM: 0.138
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-6473320-CTTT-C [0/1] rs56077837
Variant score: 0.138
Transcripts:
MCPH1:ENST00000344683.10:c.1936-4273_1936-4271del:p.(=)
Pathogenicity Data:
Best Score: 0.138149
REMM: 0.138
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-6505368-G-T [1/1]
Variant score: 0.138
Transcripts:
MCPH1:ENST00000344683.10:c.2214+5439G>T:p.(=)
Pathogenicity Data:
Best Score: 0.137976
REMM: 0.138
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-6505797-A-T [0/1] rs1352517129
Variant score: 0.137
Transcripts:
MCPH1:ENST00000344683.10:c.2214+5868A>T:p.(=)
Pathogenicity Data:
Best Score: 0.137072
REMM: 0.137
Frequency Data:
gnomAD_G_NFE: 0.0025%
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-6505794-A-AG [0/1] rs1279178990
Variant score: 0.133
Transcripts:
MCPH1:ENST00000344683.10:c.2214+5865_2214+5866insG:p.(=)
Pathogenicity Data:
Best Score: 0.133265
REMM: 0.133
Frequency Data:
gnomAD_G_NFE: 0.0025%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-6505764-A-T [0/1] rs374687711
Variant score: 0.128
Transcripts:
MCPH1:ENST00000344683.10:c.2214+5835A>T:p.(=)
Pathogenicity Data:
Best Score: 0.128296
REMM: 0.128
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-6505801-TGC-T [0/1] rs1364810171
Variant score: 0.124
Transcripts:
MCPH1:ENST00000344683.10:c.2214+5873_2214+5874del:p.(=)
Pathogenicity Data:
Best Score: 0.124306
REMM: 0.124
Frequency Data:
gnomAD_G_NFE: 0.0029%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-6505799-C-T [0/1]
Variant score: 0.117
Transcripts:
MCPH1:ENST00000344683.10:c.2214+5870C>T:p.(=)
Pathogenicity Data:
Best Score: 0.11718
REMM: 0.117
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-6505540-T-A [1/1] rs11786947
Variant score: 0.112
Transcripts:
MCPH1:ENST00000344683.10:c.2214+5611T>A:p.(=)
Pathogenicity Data:
Best Score: 0.112348
REMM: 0.112
Frequency Data:
gnomAD_G_NFE: 0.0040%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-6505765-A-C [0/1] rs377466614
Variant score: 0.107
Transcripts:
MCPH1:ENST00000344683.10:c.2214+5836A>C:p.(=)
Pathogenicity Data:
Best Score: 0.133522
REMM: 0.134
Frequency Data:
gnomAD_G_AFR: 0.0969%
gnomAD_G_AMR: 0.4777%
gnomAD_G_EAS: 0.0723%
gnomAD_G_NFE: 0.9003%
gnomAD_G_SAS: 0.4986%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-6505348-ATT-A [1/1] rs374456661
Variant score: 0.088
Transcripts:
MCPH1:ENST00000344683.10:c.2214+5420_2214+5421del:p.(=)
Pathogenicity Data:
Best Score: 0.146444
REMM: 0.146
Frequency Data:
gnomAD_G_AFR: 0.1956%
gnomAD_G_AMR: 0.5281%
gnomAD_G_EAS: 0.1287%
gnomAD_G_NFE: 1.3726%
gnomAD_G_SAS: 0.4931%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-6505763-G-T [0/1] rs370785593
Variant score: 0.084
Transcripts:
MCPH1:ENST00000344683.10:c.2214+5834G>T:p.(=)
Pathogenicity Data:
Best Score: 0.0844794
REMM: 0.084
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-6505785-T-TAC [0/1] rs1262682417
Variant score: 0.080
Transcripts:
MCPH1:ENST00000344683.10:c.2214+5856_2214+5857insAC:p.(=)
Pathogenicity Data:
Best Score: 0.0801825
REMM: 0.080
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-6505355-C-A [1/1] rs369686444
Variant score: 0.033
Transcripts:
MCPH1:ENST00000344683.10:c.2214+5426C>A:p.(=)
Pathogenicity Data:
Best Score: 0.0785687
REMM: 0.079
Frequency Data:
gnomAD_G_AFR: 0.4039%
gnomAD_G_AMR: 0.7668%
gnomAD_G_EAS: 0.1952%
gnomAD_G_NFE: 1.6569%
gnomAD_G_SAS: 0.4704%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-6515443-G-C [0/1]
Variant score: 0.007
Transcripts:
MCPH1:ENST00000344683.10:c.2214+15514G>C:p.(=)
Pathogenicity Data:
Best Score: 0.00661111
REMM: 0.007
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-6545029-G-A [0/1] rs150387881
Variant score: 0.001
Transcripts:
MCPH1:ENST00000344683.10:c.2214+45100G>A:p.(=)
Pathogenicity Data:
Best Score: 0.001
REMM: 0.001
Frequency Data:
gnomAD_G_AFR: 0.0096%
gnomAD_G_EAS: 0.0579%
gnomAD_G_NFE: 0.0162%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-6423190-C-T [1/1] rs2515534
Variant score: 0.000
Transcripts:
MCPH1:ENST00000344683.10:c.233+8307C>T:p.(=)
Pathogenicity Data:
Best Score: 1.11111E-4
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-6499786-T-G [0/1] rs2916715
Variant score: 0.000
Transcripts:
MCPH1:ENST00000344683.10:c.2137-66T>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_E_AMR: 0.0135%
gnomAD_E_NFE: 0.0048%
gnomAD_E_SAS: 0.0885%
gnomAD_G_AMR: 0.0523%
gnomAD_G_EAS: 0.0386%
gnomAD_G_NFE: 0.0103%
gnomAD_G_SAS: 0.1453%
THREE_PRIME_UTR_EXON_VARIANT SNV 8-6646913-G-A [0/1] rs113377396
Variant score: 0.000
Transcripts:
MCPH1:ENST00000344683.10:c.*3864G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.9389%
gnomAD_G_AFR: 0.1156%
gnomAD_G_AMR: 0.3141%
gnomAD_G_NFE: 0.7631%
gnomAD_G_SAS: 0.0414%
DOWNSTREAM_GENE_VARIANT SNV 8-6652529-C-T [0/1] rs577662937
Variant score: 0.000
Transcripts:
MCPH1:ENST00000344683.10::
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0073%
gnomAD_G_AMR: 0.0066%
gnomAD_G_NFE: 0.0029%
gnomAD_G_SAS: 0.0208%

TOP1MT

Exomiser Score: 0.267 (p=1.7E-1)

Phenotype Score: 0.502

Variant Score: 0.768

Phenotype matches:
Proximity score 0.502 in interactome to WRN and phenotypic similarity 0.936 to Werner syndrome associated with WRN.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.502 in interactome to WRN and phenotypic similarity 0.324 to mouse mutant of WRN.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0010876, decreased bone volume
HP:0006625, Multifocal breast carcinoma - MP:0010876, decreased bone volume
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.267 (p=1.7E-1)

Phenotype Score: 0.502

Variant Score: 0.768

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-143322519-A-AACAGGCACGCCAC [0|1] rs145270080
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.768 CONTRIBUTING VARIANT
Transcripts:
TOP1MT:ENST00000329245.9:c.961-1134_961-1133insGTGGCGTGCCTGT:p.(=)
Pathogenicity Data:
Best Score: 0.768368
REMM: 0.768
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.171 (p=2.1E-1)

Phenotype Score: 0.502

Variant Score: 0.706

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-143322519-A-AACAGGCACGCCAC [0|1] rs145270080
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.768 CONTRIBUTING VARIANT
Transcripts:
TOP1MT:ENST00000329245.9:c.961-1134_961-1133insGTGGCGTGCCTGT:p.(=)
Pathogenicity Data:
Best Score: 0.768368
REMM: 0.768
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-143322195-CCA-C [0/1] rs1273771125
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.644 CONTRIBUTING VARIANT
Transcripts:
TOP1MT:ENST00000329245.9:c.961-811_961-810del:p.(=)
Pathogenicity Data:
Best Score: 0.645506
REMM: 0.646
Frequency Data:
gnomAD_G_AFR: 0.0040%
gnomAD_G_NFE: 0.0145%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-143322257-A-ACACACATGCTCAC [1/1]
Variant score: 0.602
Transcripts:
TOP1MT:ENST00000329245.9:c.961-872_961-871insGTGAGCATGTGTG:p.(=)
Pathogenicity Data:
Best Score: 0.602345
REMM: 0.602
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 8-143318044-G-A [0/1] rs371289275
Variant score: 0.600
Transcripts:
TOP1MT:ENST00000329245.9:c.1189C>T:p.(Arg397Trp)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_NFE: 0.0041%
gnomAD_E_SAS: 0.0035%
gnomAD_G_AFR: 0.0024%
DOWNSTREAM_GENE_VARIANT DEL 8-143307519-GGCAGAGGGTCCCGCGTGGCAGAGAGGGCA-G [0|1] rs1815877050
Variant score: 0.591
Transcripts:
TOP1MT:ENST00000329245.9::
Pathogenicity Data:
Best Score: 0.598856
REMM: 0.599
Frequency Data:
gnomAD_G_AMR: 0.0872%
gnomAD_G_NFE: 0.0067%
MISSENSE_VARIANT SNV 8-143309494-G-A [0/1] rs140412370
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.583
Transcripts:
TOP1MT:ENST00000329245.9:c.1753C>T:p.(Arg585Trp)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AMR: 0.0067%
gnomAD_E_EAS: 0.1159%
gnomAD_E_NFE: 0.0043%
gnomAD_E_SAS: 0.0023%
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0065%
gnomAD_G_EAS: 0.1926%
gnomAD_G_NFE: 0.0074%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-143322263-A-G [0/1] rs377482092
Variant score: 0.570
Transcripts:
TOP1MT:ENST00000329245.9:c.961-877T>C:p.(=)
Pathogenicity Data:
Best Score: 0.569831
REMM: 0.570
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-143322182-C-CCA [0/1] rs1470887781
Variant score: 0.569
Transcripts:
TOP1MT:ENST00000329245.9:c.961-797_961-796insTG:p.(=)
Pathogenicity Data:
Best Score: 0.585117
REMM: 0.585
Frequency Data:
gnomAD_G_AFR: 0.1881%
gnomAD_G_AMR: 0.0764%
gnomAD_G_NFE: 0.0466%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-143322193-C-T [0/1] rs1266818225
Variant score: 0.510
Transcripts:
TOP1MT:ENST00000329245.9:c.961-807G>A:p.(=)
Pathogenicity Data:
Best Score: 0.525542
REMM: 0.526
Frequency Data:
gnomAD_G_AFR: 0.0416%
gnomAD_G_AMR: 0.1208%
gnomAD_G_NFE: 0.2022%
DOWNSTREAM_GENE_VARIANT DEL 8-143308132-CAGAGA-C [0|1] rs763377464
Variant score: 0.484
Transcripts:
TOP1MT:ENST00000329245.9::
Pathogenicity Data:
Best Score: 0.483759
REMM: 0.484
Frequency Data:
No frequency data
DOWNSTREAM_GENE_VARIANT DEL 8-143308353-GAGA-G [0/1] rs68021124
Variant score: 0.449
Transcripts:
TOP1MT:ENST00000329245.9::
Pathogenicity Data:
Best Score: 0.454227
REMM: 0.454
Frequency Data:
gnomAD_G_AFR: 0.0213%
gnomAD_G_AMR: 0.0795%
gnomAD_G_NFE: 0.0120%
DOWNSTREAM_GENE_VARIANT DEL 8-143307341-GAGGAA-G [0|1] rs1269278908
Variant score: 0.435
Transcripts:
TOP1MT:ENST00000329245.9::
Pathogenicity Data:
Best Score: 0.43503
REMM: 0.435
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-143322211-G-A [0/1] rs771340679
Variant score: 0.400
Transcripts:
TOP1MT:ENST00000329245.9:c.961-825C>T:p.(=)
Pathogenicity Data:
Best Score: 0.417899
REMM: 0.418
Frequency Data:
gnomAD_G_NFE: 0.0204%
gnomAD_G_SAS: 0.2747%
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-143323726-A-ACACATGCTCAC [0/1] rs879811185
Variant score: 0.392
Transcripts:
TOP1MT:ENST00000329245.9:c.960+272_960+273insGTGAGCATGTG:p.(=)
Pathogenicity Data:
Best Score: 0.405042
REMM: 0.405
Frequency Data:
gnomAD_G_AFR: 0.0035%
gnomAD_G_AMR: 0.0330%
gnomAD_G_EAS: 0.2165%
gnomAD_G_NFE: 0.0238%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-143322221-G-T [0/1] rs368241615
Variant score: 0.339
Transcripts:
TOP1MT:ENST00000329245.9:c.961-835C>A:p.(=)
Pathogenicity Data:
Best Score: 0.344491
REMM: 0.344
Frequency Data:
gnomAD_G_AFR: 0.1045%
gnomAD_G_NFE: 0.0461%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-143322839-CCA-C [0/1] rs1404326466
Variant score: 0.302
Transcripts:
TOP1MT:ENST00000329245.9:c.960+1158_960+1159del:p.(=)
Pathogenicity Data:
Best Score: 0.369417
REMM: 0.369
Frequency Data:
gnomAD_G_AFR: 0.0680%
gnomAD_G_AMR: 0.6999%
gnomAD_G_EAS: 0.8152%
gnomAD_G_NFE: 0.8535%
gnomAD_G_SAS: 0.7752%
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-143322795-C-CA [0/1] rs149788858
Variant score: 0.281
Transcripts:
TOP1MT:ENST00000329245.9:c.960+1203_960+1204insT:p.(=)
Pathogenicity Data:
Best Score: 0.627758
REMM: 0.628
Frequency Data:
gnomAD_G_AFR: 0.0910%
gnomAD_G_AMR: 0.9960%
gnomAD_G_EAS: 1.6260%
gnomAD_G_NFE: 0.8024%
DOWNSTREAM_GENE_VARIANT SNV 8-143307965-A-G [0/1] rs370467994
Variant score: 0.256
Transcripts:
TOP1MT:ENST00000329245.9::
Pathogenicity Data:
Best Score: 0.330756
REMM: 0.331
Frequency Data:
gnomAD_G_AFR: 0.1550%
gnomAD_G_AMR: 0.1168%
gnomAD_G_EAS: 0.9804%
gnomAD_G_NFE: 0.0263%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-143323066-A-G [0/1]
Variant score: 0.250
Transcripts:
TOP1MT:ENST00000329245.9:c.960+933T>C:p.(=)
Pathogenicity Data:
Best Score: 0.25044
REMM: 0.250
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-143322121-ACACACAGGCACGC-A [0/1] rs1465771984
Variant score: 0.246
Transcripts:
TOP1MT:ENST00000329245.9:c.961-748_961-736del:p.(=)
Pathogenicity Data:
Best Score: 0.627264
REMM: 0.627
Frequency Data:
gnomAD_G_AFR: 0.0655%
gnomAD_G_AMR: 0.5832%
gnomAD_G_EAS: 1.7021%
gnomAD_G_NFE: 1.0287%
gnomAD_G_SAS: 1.3889%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-143323701-G-T [0/1]
Variant score: 0.136
Transcripts:
TOP1MT:ENST00000329245.9:c.960+298C>A:p.(=)
Pathogenicity Data:
Best Score: 0.136021
REMM: 0.136
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-143323704-A-T [0/1] rs1453833902
Variant score: 0.128
Transcripts:
TOP1MT:ENST00000329245.9:c.960+295T>A:p.(=)
Pathogenicity Data:
Best Score: 0.127962
REMM: 0.128
Frequency Data:
No frequency data
DOWNSTREAM_GENE_VARIANT SNV 8-143307337-A-G [0|1] rs113483647
Variant score: 0.094
Transcripts:
TOP1MT:ENST00000329245.9::
Pathogenicity Data:
Best Score: 0.0943
REMM: 0.094
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-143325816-G-A [0/1] rs186392563
Variant score: 0.030
Transcripts:
TOP1MT:ENST00000329245.9:c.484-283C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0383639
REMM: 0.038
Frequency Data:
UK10K: 0.5157%
gnomAD_G_AFR: 0.0794%
gnomAD_G_AMR: 0.0980%
gnomAD_G_EAS: 0.0387%
gnomAD_G_NFE: 0.9414%
gnomAD_G_SAS: 0.4973%

DTNBP1

Exomiser Score: 0.266 (p=1.7E-1)

Phenotype Score: 0.501

Variant Score: 0.769

Phenotype matches:
Proximity score 0.501 in interactome to CCDC141 and phenotypic similarity 0.620 to Kallmann syndrome associated with CCDC141.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003187, Breast hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0003187, Breast hypoplasia
Known diseases:
OMIM:614076 Hermansky-Pudlak syndrome 7 - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.266 (p=1.7E-1)

Phenotype Score: 0.501

Variant Score: 0.769

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-15553594-C-CTTTTTTTTTTTTTTT [1/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.769 CONTRIBUTING VARIANT
Transcripts:
DTNBP1:ENST00000344537.10:c.512-20200_512-20199insAAAAAAAAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.769198
REMM: 0.769
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.003 (p=6.0E-1)

Phenotype Score: 0.251

Variant Score: 0.530

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-15608340-T-TATAAATAA [0/1] rs532286625
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.530 CONTRIBUTING VARIANT
Transcripts:
DTNBP1:ENST00000344537.10:c.488+6926_488+6927insTTATTTAT:p.(=)
Pathogenicity Data:
Best Score: 0.529884
REMM: 0.530
Frequency Data:
gnomAD_G_NFE: 0.0015%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-15569360-C-G [1/1] rs56273146
Variant score: 0.670
Transcripts:
DTNBP1:ENST00000344537.10:c.511+23699G>C:p.(=)
Pathogenicity Data:
Best Score: 0.669667
REMM: 0.670
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-15658374-T-A [1/1] rs12196958
Variant score: 0.575
Transcripts:
DTNBP1:ENST00000344537.10:c.56+4440A>T:p.(=)
Pathogenicity Data:
Best Score: 0.782657
REMM: 0.783
Frequency Data:
UK10K: 1.0844%
gnomAD_G_AFR: 0.2141%
gnomAD_G_AMR: 0.9159%
gnomAD_G_NFE: 0.8703%
gnomAD_G_SAS: 0.1037%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-15595250-CTTT-C [1/1] rs561001975
Variant score: 0.430
Transcripts:
DTNBP1:ENST00000344537.10:c.489-2172_489-2170del:p.(=)
Pathogenicity Data:
Best Score: 0.430346
REMM: 0.430
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-15534659-CA-C [1/1]
Variant score: 0.411
Transcripts:
DTNBP1:ENST00000344537.10:c.512-1265del:p.(=)
Pathogenicity Data:
Best Score: 0.411208
REMM: 0.411
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-15613358-T-TTC [0/1] rs1491511855
Variant score: 0.076
Transcripts:
DTNBP1:ENST00000344537.10:c.488+1908_488+1909insGA:p.(=)
Pathogenicity Data:
Best Score: 0.0762698
REMM: 0.076
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-15543484-G-A [0/1] rs1047107228
Variant score: 0.004
Transcripts:
DTNBP1:ENST00000344537.10:c.512-10089C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00366667
REMM: 0.004
Frequency Data:
gnomAD_G_AFR: 0.0169%
gnomAD_G_AMR: 0.0131%
gnomAD_G_NFE: 0.0176%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-15576265-C-T [0/1] rs1449856821
Variant score: 0.000
Transcripts:
DTNBP1:ENST00000344537.10:c.511+16794G>A:p.(=)
Pathogenicity Data:
Best Score: 2.0E-4
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0048%
gnomAD_G_NFE: 0.0015%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-15581478-G-T [0/1]
Variant score: 0.000
Transcripts:
DTNBP1:ENST00000344537.10:c.511+11581C>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data

COL11A1

Exomiser Score: 0.254 (p=1.7E-1)

Phenotype Score: 0.502

Variant Score: 0.762

Phenotype matches:
Phenotypic similarity 0.492 to Fibrochondrogenesis associated with COL11A1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000774, Narrow chest
HP:0006625, Multifocal breast carcinoma - HP:0000774, Narrow chest
Phenotypic similarity 0.326 to mouse mutant involving COL11A1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0006432, abnormal costal cartilage morphology
HP:0006625, Multifocal breast carcinoma - MP:0006432, abnormal costal cartilage morphology
Proximity score 0.502 in interactome to ITGA3 and phenotypic similarity 0.603 to Epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome associated with ITGA3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Known diseases:
OMIM:154780 Marshall syndrome - autosomal dominant
OMIM:228520 Fibrochondrogenesis 1 - autosomal recessive
OMIM:604841 Stickler syndrome, type II - autosomal dominant
OMIM:618533 Deafness, autosomal dominant 37 - autosomal dominant
ORPHA:2021 Fibrochondrogenesis - autosomal recessive
ORPHA:560 Marshall syndrome - autosomal dominant
ORPHA:90654 Stickler syndrome type 2 - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.254 (p=1.7E-1)

Phenotype Score: 0.502

Variant Score: 0.762

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.492 to ORPHA:2021 Fibrochondrogenesis
Phenotypic similarity 0.491 to OMIM:228520 Fibrochondrogenesis 1
Variants contributing to score:
SPLICE_REGION_VARIANT SNV 1-102913637-C-T [0/1] rs147637674
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:4, LB:3)
Variant score: 0.763 CONTRIBUTING VARIANT
Transcripts:
COL11A1:ENST00000370096.9:c.4032G>A:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.2909%
gnomAD_E_AFR: 0.0120%
gnomAD_E_AMR: 0.0671%
gnomAD_E_EAS: 0.0152%
gnomAD_E_NFE: 0.1349%
gnomAD_E_SAS: 0.1032%
gnomAD_G_AFR: 0.0072%
gnomAD_G_AMR: 0.0327%
gnomAD_G_EAS: 0.0386%
gnomAD_G_NFE: 0.1118%
gnomAD_G_SAS: 0.0828%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-102892150-A-T [0/1] rs568384972
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.760 CONTRIBUTING VARIANT
Transcripts:
COL11A1:ENST00000370096.9:c.4303-1646T>A:p.(=)
Pathogenicity Data:
Best Score: 0.796484
REMM: 0.796
Frequency Data:
UK10K: 0.2909%
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0262%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.1117%
gnomAD_G_SAS: 0.0828%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.001 (p=7.2E-1)

Phenotype Score: 0.502

Variant Score: 0.124

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-103065522-C-CAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.124 CONTRIBUTING VARIANT
Transcripts:
COL11A1:ENST00000370096.9:c.651+9095_651+9096insTT:p.(=)
Pathogenicity Data:
Best Score: 0.123878
REMM: 0.124
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-103006526-A-ATTTTTTTT [0/1] rs4013849
Variant score: 0.285
Transcripts:
COL11A1:ENST00000370096.9:c.1684-212_1684-211insAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.368337
REMM: 0.368
Frequency Data:
gnomAD_G_AFR: 0.9821%
gnomAD_G_AMR: 0.4357%
gnomAD_G_EAS: 0.3653%
gnomAD_G_NFE: 0.5570%
gnomAD_G_SAS: 0.3800%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-103025452-G-A [0/1] rs41292531
ClinVar: LIKELY_BENIGN (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.186
Transcripts:
COL11A1:ENST00000370096.9:c.990+69C>T:p.(=)
Pathogenicity Data:
Best Score: 0.627147
REMM: 0.627
Frequency Data:
UK10K: 1.8249%
gnomAD_E_AFR: 0.1992%
gnomAD_E_AMR: 0.4912%
gnomAD_E_EAS: 0.0055%
gnomAD_E_NFE: 1.6610%
gnomAD_E_SAS: 1.7961%
gnomAD_G_AFR: 0.2309%
gnomAD_G_AMR: 0.6344%
gnomAD_G_NFE: 1.5175%
gnomAD_G_SAS: 1.5114%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-102952621-A-G [0/1] rs72683282
Variant score: 0.182
Transcripts:
COL11A1:ENST00000370096.9:c.3169-5665T>C:p.(=)
Pathogenicity Data:
Best Score: 0.690791
REMM: 0.691
Frequency Data:
UK10K: 1.6133%
gnomAD_G_AFR: 0.2332%
gnomAD_G_AMR: 0.6339%
gnomAD_G_NFE: 1.5203%
gnomAD_G_SAS: 1.8634%
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-103046277-C-CCTGTTGTTCCCTGA [1/1]
Variant score: 0.099
Transcripts:
COL11A1:ENST00000370096.9:c.652-15034_652-15033insTCAGGGAACAACAG:p.(=)
Pathogenicity Data:
Best Score: 0.0986024
REMM: 0.099
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-103059552-G-GA [0/1] rs149695656
Variant score: 0.081
Transcripts:
COL11A1:ENST00000370096.9:c.651+15065_651+15066insT:p.(=)
Pathogenicity Data:
Best Score: 0.264778
REMM: 0.265
Frequency Data:
UK10K: 1.8117%
gnomAD_G_AFR: 0.2286%
gnomAD_G_AMR: 0.6218%
gnomAD_G_NFE: 1.4878%
gnomAD_G_SAS: 1.0973%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-102946068-A-G [0/1]
Variant score: 0.039
Transcripts:
COL11A1:ENST00000370096.9:c.3276+781T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0392095
REMM: 0.039
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-102903569-A-T [0/1] rs1048126391
Variant score: 0.002
Transcripts:
COL11A1:ENST00000370096.9:c.4087-4575T>A:p.(=)
Pathogenicity Data:
Best Score: 0.00245833
REMM: 0.002
Frequency Data:
gnomAD_G_NFE: 0.0059%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-102933327-A-G [1/1] rs9793259
Variant score: 0.001
Transcripts:
COL11A1:ENST00000370096.9:c.3600+1122T>C:p.(=)
Pathogenicity Data:
Best Score: 6.0E-4
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-102929203-C-T [0/1] rs36177555
Variant score: 0.000
Transcripts:
COL11A1:ENST00000370096.9:c.3600+5246G>A:p.(=)
Pathogenicity Data:
Best Score: 4.5E-4
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-102945971-C-T [1/1] rs7414903
Variant score: 0.000
Transcripts:
COL11A1:ENST00000370096.9:c.3276+878G>A:p.(=)
Pathogenicity Data:
Best Score: 2.0E-4
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-102888556-C-T [0/1] rs199882962
Variant score: 0.000
Transcripts:
COL11A1:ENST00000370096.9:c.4608+21G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.0529%
gnomAD_E_AFR: 0.0030%
gnomAD_E_AMR: 0.0381%
gnomAD_E_NFE: 0.0261%
gnomAD_E_SAS: 0.0267%
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0196%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.0294%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-103104763-T-C [0/1] rs151202644
Variant score: 0.000
Transcripts:
COL11A1:ENST00000370096.9:c.106+3310A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.2645%
gnomAD_G_AFR: 0.0144%
gnomAD_G_AMR: 0.0262%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.1162%
gnomAD_G_SAS: 0.1244%

SRD5A3

Exomiser Score: 0.252 (p=1.7E-1)

Phenotype Score: 0.643

Variant Score: 0.601

Phenotype matches:
Phenotypic similarity 0.643 to Congenital disorder of glycosylation, type Iq associated with SRD5A3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Proximity score 0.516 in interactome to LHB and phenotypic similarity 0.614 to Hypogonadotropic hypogonadism 23 with or without anosmia associated with LHB.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Known diseases:
OMIM:612379 Congenital disorder of glycosylation, type Iq - autosomal recessive
OMIM:612713 Kahrizi syndrome - autosomal recessive
ORPHA:324737 SRD5A3-CDG - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.252 (p=1.7E-1)

Phenotype Score: 0.643

Variant Score: 0.601

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.643 to OMIM:612379 Congenital disorder of glycosylation, type Iq
Phenotypic similarity 0.460 to OMIM:612713 Kahrizi syndrome
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-55351876-T-C [0/1] rs548593560
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PP4]
Variant score: 0.658 CONTRIBUTING VARIANT
Transcripts:
SRD5A3:ENST00000264228.9:c.221+5319T>C:p.(=)
Pathogenicity Data:
Best Score: 0.697051
REMM: 0.697
Frequency Data:
UK10K: 0.1058%
gnomAD_E_AFR: 0.0288%
gnomAD_E_AMR: 0.0781%
gnomAD_E_EAS: 0.0090%
gnomAD_E_NFE: 0.0871%
gnomAD_E_SAS: 0.3497%
gnomAD_G_AFR: 0.0529%
gnomAD_G_AMR: 0.1633%
gnomAD_G_NFE: 0.0956%
gnomAD_G_SAS: 0.3314%
UPSTREAM_GENE_VARIANT DEL 4-55343115-CAAAAAAAAAAAAAAAAAAAAAA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting, PP4]
Variant score: 0.545 CONTRIBUTING VARIANT
Transcripts:
SRD5A3:ENST00000264228.9::
Pathogenicity Data:
Best Score: 0.544905
REMM: 0.545
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.004 (p=5.8E-1)

Phenotype Score: 0.258

Variant Score: 0.545

No phenotype matches to diseases with this MOI.
Variants contributing to score:
UPSTREAM_GENE_VARIANT DEL 4-55343115-CAAAAAAAAAAAAAAAAAAAAAA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.545 CONTRIBUTING VARIANT
Transcripts:
SRD5A3:ENST00000264228.9::
Pathogenicity Data:
Best Score: 0.544905
REMM: 0.545
Frequency Data:
No frequency data
Other passed variants:
UPSTREAM_GENE_VARIANT DEL 4-55343115-CAAAAAAAAA-C [0/1]
Variant score: 0.532
Transcripts:
SRD5A3:ENST00000264228.9::
Pathogenicity Data:
Best Score: 0.53166
REMM: 0.532
Frequency Data:
No frequency data
INTERGENIC_VARIANT INS 4-55378341-C-CAAAAAA [0/1] rs760337461
Variant score: 0.329
Transcripts:
SRD5A3:ENST00000264228.9::
Pathogenicity Data:
Best Score: 0.331349
REMM: 0.331
Frequency Data:
gnomAD_G_AFR: 0.0549%
gnomAD_G_NFE: 0.0063%
INTERGENIC_VARIANT INS 4-55340187-C-CAAAAAA [0/1]
Variant score: 0.239
Transcripts:
SRD5A3:ENST00000264228.9::
Pathogenicity Data:
Best Score: 0.239355
REMM: 0.239
Frequency Data:
No frequency data
INTERGENIC_VARIANT INS 4-55378360-A-AAG [0/1] rs1553883437
Variant score: 0.233
Transcripts:
SRD5A3:ENST00000264228.9::
Pathogenicity Data:
Best Score: 0.233474
REMM: 0.233
Frequency Data:
No frequency data
INTERGENIC_VARIANT INS 4-55378358-A-AG [0/1] rs60919203
Variant score: 0.213
Transcripts:
SRD5A3:ENST00000264228.9::
Pathogenicity Data:
Best Score: 0.213336
REMM: 0.213
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 4-55340217-A-C [0/1] rs547481815
Variant score: 0.204
Transcripts:
SRD5A3:ENST00000264228.9::
Pathogenicity Data:
Best Score: 0.324362
REMM: 0.324
Frequency Data:
gnomAD_G_AFR: 0.5387%
gnomAD_G_AMR: 0.5285%
gnomAD_G_EAS: 0.0198%
gnomAD_G_NFE: 0.5659%
gnomAD_G_SAS: 1.3215%
INTERGENIC_VARIANT SNV 4-55334090-A-G [0/1]
Variant score: 0.145
Transcripts:
SRD5A3:ENST00000264228.9::
Pathogenicity Data:
Best Score: 0.1448
REMM: 0.145
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 4-55360687-C-CT [0/1]
Variant score: 0.019
Transcripts:
SRD5A3:ENST00000264228.9:c.364+1199_364+1200insT:p.(=)
Pathogenicity Data:
Best Score: 0.0190821
REMM: 0.019
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 4-55358555-A-AAG [0/1] rs1553881762
Variant score: 0.006
Transcripts:
SRD5A3:ENST00000264228.9:c.222-791_222-790insAG:p.(=)
Pathogenicity Data:
Best Score: 0.0057369
REMM: 0.006
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 4-55390761-C-T [0/1] rs114845988
Variant score: 0.000
Transcripts:
SRD5A3:ENST00000264228.9::
Pathogenicity Data:
Best Score: 0.00197619
REMM: 0.002
Frequency Data:
UK10K: 0.7670%
gnomAD_G_AFR: 0.6371%
gnomAD_G_AMR: 0.8720%
gnomAD_G_EAS: 0.0390%
gnomAD_G_NFE: 0.7860%
gnomAD_G_SAS: 1.8947%
INTERGENIC_VARIANT SNV 4-55392844-G-T [0/1] rs147295245
Variant score: 0.000
Transcripts:
SRD5A3:ENST00000264228.9::
Pathogenicity Data:
Best Score: 8.47222E-4
REMM: 0.001
Frequency Data:
UK10K: 0.7670%
gnomAD_G_AFR: 0.2185%
gnomAD_G_AMR: 0.8546%
gnomAD_G_EAS: 0.0391%
gnomAD_G_NFE: 0.7686%
gnomAD_G_SAS: 1.8773%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-55360688-G-T [0/1] rs79146775
Variant score: 0.000
Transcripts:
SRD5A3:ENST00000264228.9:c.364+1200G>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0810%
gnomAD_G_AMR: 0.0149%
gnomAD_G_EAS: 0.0434%
gnomAD_G_NFE: 0.0232%
gnomAD_G_SAS: 0.0484%

CDK5RAP2

Exomiser Score: 0.241 (p=1.8E-1)

Phenotype Score: 0.503

Variant Score: 0.753

Phenotype matches:
Phenotypic similarity 0.368 to mouse mutant involving CDK5RAP2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000160, kyphosis
HP:0006625, Multifocal breast carcinoma - MP:0000160, kyphosis
Proximity score 0.503 in interactome to ALMS1 and phenotypic similarity 0.614 to Alstrom syndrome associated with ALMS1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Known diseases:
OMIM:604804 Microcephaly 3, primary, autosomal recessive - autosomal recessive
ORPHA:2512 Autosomal recessive primary microcephaly - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.241 (p=1.8E-1)

Phenotype Score: 0.503

Variant Score: 0.753

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-120407519-G-T [0/1] rs759151997
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.915 CONTRIBUTING VARIANT
Transcripts:
CDK5RAP2:ENST00000349780.9:c.4727-271C>A:p.(=)
Pathogenicity Data:
Best Score: 0.930657
REMM: 0.931
Frequency Data:
UK10K: 0.0397%
gnomAD_E_AMR: 0.0389%
gnomAD_E_NFE: 0.0437%
gnomAD_E_SAS: 0.1188%
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0327%
gnomAD_G_NFE: 0.0368%
gnomAD_G_SAS: 0.0830%
MISSENSE_VARIANT SNV 9-120527882-G-A [0/1] rs145272328
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:3, LB:3)
Variant score: 0.591 CONTRIBUTING VARIANT
Transcripts:
CDK5RAP2:ENST00000349780.9:c.923C>T:p.(Thr308Ile)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.0132%
gnomAD_E_AFR: 0.0030%
gnomAD_E_AMR: 0.0246%
gnomAD_E_NFE: 0.0273%
gnomAD_E_SAS: 0.1032%
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0327%
gnomAD_G_NFE: 0.0323%
gnomAD_G_SAS: 0.0830%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.000 (p=8.1E-1)

Phenotype Score: 0.251

Variant Score: 0.316

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-120496703-T-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.316 CONTRIBUTING VARIANT
Transcripts:
CDK5RAP2:ENST00000349780.9:c.1312-5226A>G:p.(=)
Pathogenicity Data:
Best Score: 0.315855
REMM: 0.316
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 9-120507942-AATAT-A [1/1] rs1157642617
Variant score: 0.369
Transcripts:
CDK5RAP2:ENST00000349780.9:c.1311+10481_1311+10484del:p.(=)
Pathogenicity Data:
Best Score: 0.368977
REMM: 0.369
Frequency Data:
No frequency data
REGULATORY_REGION_VARIANT INS 9-120221744-T-TAAAAAAAAA [1/1]
Variant score: 0.329
Transcripts:
CDK5RAP2:ENST00000349780.9::
Pathogenicity Data:
Best Score: 0.329176
REMM: 0.329
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-120535205-G-A [0/1] rs747525974
Variant score: 0.046
Transcripts:
CDK5RAP2:ENST00000349780.9:c.662+1167C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0462909
REMM: 0.046
Frequency Data:
UK10K: 0.0264%
gnomAD_G_AFR: 0.0096%
gnomAD_G_AMR: 0.0327%
gnomAD_G_NFE: 0.0338%
gnomAD_G_SAS: 0.0829%
CODING_TRANSCRIPT_INTRON_VARIANT INS 9-120558371-C-CAAAA [0/1]
Variant score: 0.026
Transcripts:
CDK5RAP2:ENST00000349780.9:c.196-7470_196-7469insTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.0263806
REMM: 0.026
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-120441816-T-C [0/1] rs757040313
Variant score: 0.000
Transcripts:
CDK5RAP2:ENST00000349780.9:c.3148+1804A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.0264%
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0327%
gnomAD_G_NFE: 0.0367%
gnomAD_G_SAS: 0.0828%

TRIO

Exomiser Score: 0.240 (p=1.8E-1)

Phenotype Score: 0.503

Variant Score: 0.752

Phenotype matches:
Phenotypic similarity 0.444 to Micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome associated with TRIO.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000767, Pectus excavatum
HP:0006625, Multifocal breast carcinoma - HP:0000767, Pectus excavatum
Proximity score 0.503 in interactome to ARHGAP31 and phenotypic similarity 0.607 to Adams-Oliver syndrome 1 associated with ARHGAP31.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0002558, Supernumerary nipple
HP:0006625, Multifocal breast carcinoma - HP:0002558, Supernumerary nipple
Known diseases:
OMIM:617061 Intellectual developmental disorder, autosomal dominant 44, with microcephaly - autosomal dominant
OMIM:618825 Intellectual developmental disorder, autosomal dominant 63, with macrocephaly - autosomal dominant
ORPHA:476126 Micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.240 (p=1.8E-1)

Phenotype Score: 0.503

Variant Score: 0.752

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.444 to ORPHA:476126 Micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome
Phenotypic similarity 0.434 to OMIM:617061 Intellectual developmental disorder, autosomal dominant 44, with microcephaly
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-14361786-A-G [0/1] rs963457475
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.752 CONTRIBUTING VARIANT
Transcripts:
TRIO:ENST00000344204.9:c.2392-1946A>G:p.(=)
Pathogenicity Data:
Best Score: 0.753823
REMM: 0.754
Frequency Data:
gnomAD_G_NFE: 0.0176%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.035 (p=3.5E-1)

Phenotype Score: 0.251

Variant Score: 0.802

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-14210967-C-T [0/1] rs542700244
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.808 CONTRIBUTING VARIANT
Transcripts:
TRIO:ENST00000344204.9:c.158-59858C>T:p.(=)
Pathogenicity Data:
Best Score: 0.928634
REMM: 0.929
Frequency Data:
UK10K: 0.2645%
gnomAD_G_AFR: 0.0434%
gnomAD_G_AMR: 0.6744%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.3499%
gnomAD_G_SAS: 0.1453%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-14148980-G-A [0/1] rs143136855
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.797 CONTRIBUTING VARIANT
Transcripts:
TRIO:ENST00000344204.9:c.157+5098G>A:p.(=)
Pathogenicity Data:
Best Score: 0.84579
REMM: 0.846
Frequency Data:
UK10K: 0.2645%
gnomAD_G_AFR: 0.0409%
gnomAD_G_AMR: 0.2940%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.3528%
gnomAD_G_SAS: 0.1450%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 5-14161084-ATTT-A [0/1] rs989398777
Variant score: 0.743
Transcripts:
TRIO:ENST00000344204.9:c.157+17203_157+17205del:p.(=)
Pathogenicity Data:
Best Score: 0.744933
REMM: 0.745
Frequency Data:
gnomAD_G_NFE: 0.0162%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-14150906-T-G [0/1]
Variant score: 0.716
Transcripts:
TRIO:ENST00000344204.9:c.157+7024T>G:p.(=)
Pathogenicity Data:
Best Score: 0.715752
REMM: 0.716
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 5-14202319-TTTTTTTTTTTTG-T [0/1] rs1448919412
Variant score: 0.690
Transcripts:
TRIO:ENST00000344204.9:c.157+58438_157+58449del:p.(=)
Pathogenicity Data:
Best Score: 0.689586
REMM: 0.690
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-14498381-C-T [0/1] rs745755102
Variant score: 0.673
Transcripts:
TRIO:ENST00000344204.9:c.8210+130C>T:p.(=)
Pathogenicity Data:
Best Score: 0.680316
REMM: 0.680
Frequency Data:
UK10K: 0.0264%
gnomAD_E_AFR: 0.0033%
gnomAD_E_AMR: 0.0237%
gnomAD_E_EAS: 0.0084%
gnomAD_E_NFE: 0.0369%
gnomAD_E_SAS: 0.0768%
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0392%
gnomAD_G_NFE: 0.0470%
MISSENSE_VARIANT SNV 5-14487557-G-T [0/1] rs892410126
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:1, LB:2)
Variant score: 0.593
Transcripts:
TRIO:ENST00000344204.9:c.6929G>T:p.(Gly2310Val)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_NFE: 0.0156%
gnomAD_E_SAS: 0.0771%
gnomAD_G_AFR: 0.0049%
gnomAD_G_AMR: 0.0338%
gnomAD_G_NFE: 0.0272%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-14371203-A-T [0/1] rs186496240
Variant score: 0.529
Transcripts:
TRIO:ENST00000344204.9:c.3216+1680A>T:p.(=)
Pathogenicity Data:
Best Score: 0.686382
REMM: 0.686
Frequency Data:
UK10K: 0.9918%
gnomAD_G_AFR: 0.1443%
gnomAD_G_AMR: 0.0980%
gnomAD_G_NFE: 0.8188%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-14233792-G-A [0/1] rs1044985931
Variant score: 0.527
Transcripts:
TRIO:ENST00000344204.9:c.158-37033G>A:p.(=)
Pathogenicity Data:
Best Score: 0.528384
REMM: 0.528
Frequency Data:
gnomAD_G_NFE: 0.0162%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 5-14500888-CA-C [0/1] rs34729667
Variant score: 0.474
Transcripts:
TRIO:ENST00000344204.9:c.8333-1690del:p.(=)
Pathogenicity Data:
Best Score: 0.473763
REMM: 0.474
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-14500050-C-A [0/1]
Variant score: 0.385
Transcripts:
TRIO:ENST00000344204.9:c.8332+1410C>A:p.(=)
Pathogenicity Data:
Best Score: 0.385208
REMM: 0.385
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-14347341-T-C [0/1] rs256422
Variant score: 0.354
Transcripts:
TRIO:ENST00000344204.9:c.2046+10614T>C:p.(=)
Pathogenicity Data:
Best Score: 0.381899
REMM: 0.382
Frequency Data:
gnomAD_G_AFR: 0.3172%
gnomAD_G_AMR: 0.4282%
gnomAD_G_EAS: 0.3106%
gnomAD_G_NFE: 0.3460%
gnomAD_G_SAS: 0.3180%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-14455511-T-C [0/1] rs889034869
Variant score: 0.327
Transcripts:
TRIO:ENST00000344204.9:c.5204-5508T>C:p.(=)
Pathogenicity Data:
Best Score: 0.327338
REMM: 0.327
Frequency Data:
gnomAD_G_NFE: 0.0044%
CODING_TRANSCRIPT_INTRON_VARIANT INS 5-14421227-A-ATTTATTTTAT [0/1] rs77834736
Variant score: 0.235
Transcripts:
TRIO:ENST00000344204.9:c.5203+1206_5203+1207insTTTATTTTAT:p.(=)
Pathogenicity Data:
Best Score: 0.235252
REMM: 0.235
Frequency Data:
No frequency data
INTERGENIC_VARIANT INS 5-14137172-C-CT [0/1] rs578011439
Variant score: 0.205
Transcripts:
TRIO:ENST00000344204.9::
Pathogenicity Data:
Best Score: 0.389595
REMM: 0.390
Frequency Data:
gnomAD_G_AFR: 0.2889%
gnomAD_G_AMR: 0.9227%
gnomAD_G_EAS: 0.2019%
gnomAD_G_NFE: 0.7244%
gnomAD_G_SAS: 1.5044%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-14264003-G-A [0/1] rs1020542335
Variant score: 0.184
Transcripts:
TRIO:ENST00000344204.9:c.158-6822G>A:p.(=)
Pathogenicity Data:
Best Score: 0.184961
REMM: 0.185
Frequency Data:
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0523%
gnomAD_G_NFE: 0.0338%
gnomAD_G_SAS: 0.0207%
DOWNSTREAM_GENE_VARIANT DEL 5-14511677-CTATATATATATATA-C [0/1] rs543621706
Variant score: 0.088
Transcripts:
TRIO:ENST00000344204.9::
Pathogenicity Data:
Best Score: 0.14291
REMM: 0.143
Frequency Data:
gnomAD_G_AFR: 1.1180%
gnomAD_G_AMR: 1.1294%
gnomAD_G_EAS: 1.3441%
gnomAD_G_NFE: 1.1604%
gnomAD_G_SAS: 0.6173%
CODING_TRANSCRIPT_INTRON_VARIANT INS 5-14396443-C-CTTT [0/1] rs1173121592
Variant score: 0.054
Transcripts:
TRIO:ENST00000344204.9:c.4312-600_4312-599insTTT:p.(=)
Pathogenicity Data:
Best Score: 0.0548325
REMM: 0.055
Frequency Data:
gnomAD_G_AFR: 0.0475%
gnomAD_G_AMR: 0.0478%
gnomAD_G_NFE: 0.1037%
CODING_TRANSCRIPT_INTRON_VARIANT INS 5-14396443-C-CT [0/1] rs1173121592
Variant score: 0.054
Transcripts:
TRIO:ENST00000344204.9:c.4312-600_4312-599insT:p.(=)
Pathogenicity Data:
Best Score: 0.0548325
REMM: 0.055
Frequency Data:
gnomAD_G_AFR: 0.0554%
gnomAD_G_AMR: 0.0955%
gnomAD_G_NFE: 0.1037%
gnomAD_G_SAS: 0.1548%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-14472487-A-G [0/1] rs773883149
Variant score: 0.034
Transcripts:
TRIO:ENST00000344204.9:c.5913-105A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0347056
REMM: 0.035
Frequency Data:
UK10K: 0.0132%
gnomAD_E_AFR: 0.0043%
gnomAD_E_AMR: 0.0612%
gnomAD_E_NFE: 0.0425%
gnomAD_E_SAS: 0.0682%
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0458%
gnomAD_G_NFE: 0.0441%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-14217485-T-C [0/1] rs1002813051
Variant score: 0.010
Transcripts:
TRIO:ENST00000344204.9:c.158-53340T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0100798
REMM: 0.010
Frequency Data:
gnomAD_G_AFR: 0.0024%
INTERGENIC_VARIANT SNV 5-14125418-A-G [0/1] rs968388288
Variant score: 0.006
Transcripts:
TRIO:ENST00000344204.9::
Pathogenicity Data:
Best Score: 0.00611111
REMM: 0.006
Frequency Data:
gnomAD_G_NFE: 0.0044%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-14280734-A-G [0/1] rs921235818
Variant score: 0.004
Transcripts:
TRIO:ENST00000344204.9:c.347+298A>G:p.(=)
Pathogenicity Data:
Best Score: 0.00417183
REMM: 0.004
Frequency Data:
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0523%
gnomAD_G_NFE: 0.0338%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-14230869-T-C [0/1] rs141806182
Variant score: 0.003
Transcripts:
TRIO:ENST00000344204.9:c.158-39956T>C:p.(=)
Pathogenicity Data:
Best Score: 0.00370833
REMM: 0.004
Frequency Data:
UK10K: 0.2777%
gnomAD_G_AFR: 0.0433%
gnomAD_G_AMR: 0.6797%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.3469%
gnomAD_G_SAS: 0.1243%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-14347714-C-T [0/1] rs1210035350
Variant score: 0.002
Transcripts:
TRIO:ENST00000344204.9:c.2047-10464C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00235238
REMM: 0.002
Frequency Data:
gnomAD_G_NFE: 0.0015%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-14222069-G-A [0|1] rs895675159
Variant score: 0.001
Transcripts:
TRIO:ENST00000344204.9:c.158-48756G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0014
REMM: 0.001
Frequency Data:
gnomAD_G_AFR: 0.0024%
gnomAD_G_NFE: 0.0118%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-14290091-C-T [0/1] rs935979101
Variant score: 0.000
Transcripts:
TRIO:ENST00000344204.9:c.541-625C>T:p.(=)
Pathogenicity Data:
Best Score: 4.0E-4
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0523%
gnomAD_G_NFE: 0.0368%
gnomAD_G_SAS: 0.0208%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-14199222-T-C [0/1]
Variant score: 0.000
Transcripts:
TRIO:ENST00000344204.9:c.157+55340T>C:p.(=)
Pathogenicity Data:
Best Score: 2.5E-4
REMM: 0.000
Frequency Data:
No frequency data

CDC73

Exomiser Score: 0.229 (p=1.8E-1)

Phenotype Score: 0.503

Variant Score: 0.746

Phenotype matches:
Phenotypic similarity 0.300 to mouse mutant involving CDC73.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000454, abnormal jaw morphology
HP:0006625, Multifocal breast carcinoma - MP:0000454, abnormal jaw morphology
Proximity score 0.503 in interactome to MEN1 and phenotypic similarity 0.630 to Pituitary gigantism associated with MEN1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0100829, Galactorrhea
HP:0006625, Multifocal breast carcinoma - HP:0100829, Galactorrhea
Known diseases:
OMIM:145000 Hyperparathyroidism, familial primary - autosomal dominant
OMIM:145001 Parathyroid adenoma with cystic changes - autosomal dominant
OMIM:608266 Parathyroid carcinoma - autosomal dominant
ORPHA:143 Parathyroid carcinoma (unconfirmed)
ORPHA:99879 Familial isolated hyperparathyroidism - autosomal dominant
ORPHA:99880 Hyperparathyroidism-jaw tumor syndrome - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.229 (p=1.8E-1)

Phenotype Score: 0.503

Variant Score: 0.746

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-193143886-G-A [0/1] rs572273249
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.746 CONTRIBUTING VARIANT
Transcripts:
CDC73:ENST00000367435.5:c.729+1820G>A:p.(=)
Pathogenicity Data:
Best Score: 0.750409
REMM: 0.750
Frequency Data:
UK10K: 0.0397%
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0131%
gnomAD_G_NFE: 0.0441%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.034 (p=3.6E-1)

Phenotype Score: 0.251

Variant Score: 0.796

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-193203240-T-C [0/1] rs115453848
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.847 CONTRIBUTING VARIANT
Transcripts:
CDC73:ENST00000367435.5:c.973-555T>C:p.(=)
Pathogenicity Data:
Best Score: 0.881362
REMM: 0.881
Frequency Data:
UK10K: 0.0397%
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.2550%
gnomAD_G_NFE: 0.0765%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-193143886-G-A [0/1] rs572273249
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.746 CONTRIBUTING VARIANT
Transcripts:
CDC73:ENST00000367435.5:c.729+1820G>A:p.(=)
Pathogenicity Data:
Best Score: 0.750409
REMM: 0.750
Frequency Data:
UK10K: 0.0397%
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0131%
gnomAD_G_NFE: 0.0441%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-193145729-T-C [0/1] rs983299809
Variant score: 0.635
Transcripts:
CDC73:ENST00000367435.5:c.730-2138T>C:p.(=)
Pathogenicity Data:
Best Score: 0.635197
REMM: 0.635
Frequency Data:
gnomAD_G_NFE: 0.0015%
INTERGENIC_VARIANT DEL 1-193266088-GA-G [0/1] rs748683412
Variant score: 0.524
Transcripts:
CDC73:ENST00000367435.5::
Pathogenicity Data:
Best Score: 0.545435
REMM: 0.545
Frequency Data:
UK10K: 0.0397%
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.2548%
gnomAD_G_NFE: 0.0779%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-193148833-TG-T [0/1] rs148471707
Variant score: 0.422
Transcripts:
CDC73:ENST00000367435.5:c.828+869del:p.(=)
Pathogenicity Data:
Best Score: 0.587396
REMM: 0.587
Frequency Data:
gnomAD_G_AFR: 0.1256%
gnomAD_G_AMR: 0.6838%
gnomAD_G_NFE: 0.7262%
gnomAD_G_SAS: 1.1269%
INTERGENIC_VARIANT DEL 1-193109522-GA-G [0/1] rs71111448
Variant score: 0.407
Transcripts:
CDC73:ENST00000367435.5::
Pathogenicity Data:
Best Score: 0.423592
REMM: 0.424
Frequency Data:
gnomAD_G_AFR: 0.1603%
gnomAD_G_AMR: 0.1280%
gnomAD_G_EAS: 0.2496%
gnomAD_G_NFE: 0.1659%
gnomAD_G_SAS: 0.2561%
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-193144112-C-CAAAAAAAA [0/1]
Variant score: 0.305
Transcripts:
CDC73:ENST00000367435.5:c.729+2046_729+2047insAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.30452
REMM: 0.305
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-193162031-C-T [1/1] rs189317103
Variant score: 0.270
Transcripts:
CDC73:ENST00000367435.5:c.972+9587C>T:p.(=)
Pathogenicity Data:
Best Score: 0.270368
REMM: 0.270
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-193162213-T-A [0/1]
Variant score: 0.262
Transcripts:
CDC73:ENST00000367435.5:c.972+9769T>A:p.(=)
Pathogenicity Data:
Best Score: 0.261685
REMM: 0.262
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-193162205-AAT-A [0/1] rs1491188272
Variant score: 0.258
Transcripts:
CDC73:ENST00000367435.5:c.972+9762_972+9763del:p.(=)
Pathogenicity Data:
Best Score: 0.257829
REMM: 0.258
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-193161676-AATAT-A [1/1]
Variant score: 0.241
Transcripts:
CDC73:ENST00000367435.5:c.972+9233_972+9236del:p.(=)
Pathogenicity Data:
Best Score: 0.241362
REMM: 0.241
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-193162297-TATATACTATATATTATATATC-T [0/1] rs1311236453
Variant score: 0.231
Transcripts:
CDC73:ENST00000367435.5:c.972+9854_972+9874del:p.(=)
Pathogenicity Data:
Best Score: 0.230507
REMM: 0.231
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-193162277-A-G [0/1] rs188621782
Variant score: 0.228
Transcripts:
CDC73:ENST00000367435.5:c.972+9833A>G:p.(=)
Pathogenicity Data:
Best Score: 0.228212
REMM: 0.228
Frequency Data:
gnomAD_G_NFE: 0.0016%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-193161715-AATATAATATATATAAT-A [1/1]
Variant score: 0.223
Transcripts:
CDC73:ENST00000367435.5:c.972+9272_972+9287del:p.(=)
Pathogenicity Data:
Best Score: 0.223421
REMM: 0.223
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-193162083-C-T [1/1] rs111214189
Variant score: 0.191
Transcripts:
CDC73:ENST00000367435.5:c.972+9639C>T:p.(=)
Pathogenicity Data:
Best Score: 0.208096
REMM: 0.208
Frequency Data:
gnomAD_G_AMR: 0.4717%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-193162265-A-G [0/1] rs185322964
Variant score: 0.186
Transcripts:
CDC73:ENST00000367435.5:c.972+9821A>G:p.(=)
Pathogenicity Data:
Best Score: 0.191418
REMM: 0.191
Frequency Data:
gnomAD_G_AFR: 0.0765%
gnomAD_G_AMR: 0.2014%
gnomAD_G_EAS: 0.1342%
gnomAD_G_NFE: 0.1446%
gnomAD_G_SAS: 0.0946%
INTERGENIC_VARIANT DEL 1-193265208-ATT-A [0/1] rs796757045
Variant score: 0.173
Transcripts:
CDC73:ENST00000367435.5::
Pathogenicity Data:
Best Score: 0.17256
REMM: 0.173
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 1-193265208-ATTT-A [0/1]
Variant score: 0.173
Transcripts:
CDC73:ENST00000367435.5::
Pathogenicity Data:
Best Score: 0.17256
REMM: 0.173
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-193162057-C-T [1/1] rs193088070
Variant score: 0.164
Transcripts:
CDC73:ENST00000367435.5:c.972+9613C>T:p.(=)
Pathogenicity Data:
Best Score: 0.199882
REMM: 0.200
Frequency Data:
gnomAD_G_AFR: 0.0949%
gnomAD_G_AMR: 0.8475%
gnomAD_G_NFE: 0.0347%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-193161771-C-T [1/1] rs187236499
Variant score: 0.083
Transcripts:
CDC73:ENST00000367435.5:c.972+9327C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0837079
REMM: 0.084
Frequency Data:
gnomAD_G_NFE: 0.0281%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-193204352-C-T [0/1] rs150293139
Variant score: 0.061
Transcripts:
CDC73:ENST00000367435.5:c.1030+500C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0826544
REMM: 0.083
Frequency Data:
UK10K: 0.6876%
gnomAD_G_AFR: 0.1177%
gnomAD_G_AMR: 0.6711%
gnomAD_G_NFE: 0.7177%
gnomAD_G_SAS: 1.0638%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-193162295-T-A [0/1] rs537571978
Variant score: 0.047
Transcripts:
CDC73:ENST00000367435.5:c.972+9851T>A:p.(=)
Pathogenicity Data:
Best Score: 0.0502762
REMM: 0.050
Frequency Data:
gnomAD_G_AFR: 0.1553%
gnomAD_G_AMR: 0.1006%
gnomAD_G_EAS: 0.0632%
gnomAD_G_NFE: 0.1424%
gnomAD_G_SAS: 0.4390%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-193162333-C-T [0/1] rs553674204
Variant score: 0.031
Transcripts:
CDC73:ENST00000367435.5:c.972+9889C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0333218
REMM: 0.033
Frequency Data:
gnomAD_G_AFR: 0.1554%
gnomAD_G_AMR: 0.0994%
gnomAD_G_NFE: 0.1445%
gnomAD_G_SAS: 0.4792%
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-193205208-C-CTT [0/1]
Variant score: 0.023
Transcripts:
CDC73:ENST00000367435.5:c.1030+1356_1030+1357insTT:p.(=)
Pathogenicity Data:
Best Score: 0.0230159
REMM: 0.023
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-193234267-T-TTATAATATATATAATTTATTATATATATTATATATATAATATA [0/1] rs35586186
Variant score: 0.017
Transcripts:
CDC73:ENST00000367435.5:c.1316+1113_1316+1114insTATAATATATATAATTTATTATATATATTATATATATAATATA:p.(=)
Pathogenicity Data:
Best Score: 0.0171706
REMM: 0.017
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT INS 1-193117832-T-TCACACACA [0/1] rs1246537092
Variant score: 0.002
Transcripts:
CDC73:ENST00000367435.5::
Pathogenicity Data:
Best Score: 0.001625
REMM: 0.002
Frequency Data:
gnomAD_G_AFR: 0.0790%
gnomAD_G_AMR: 0.0124%
gnomAD_G_EAS: 0.0377%
gnomAD_G_NFE: 0.0341%
gnomAD_G_SAS: 0.2037%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-193220157-CTT-C [0/1] rs776793164
Variant score: 0.000
Transcripts:
CDC73:ENST00000367435.5:c.1154+7681_1154+7682del:p.(=)
Pathogenicity Data:
Best Score: 2.22222E-4
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.1564%
gnomAD_G_AMR: 0.4430%
gnomAD_G_NFE: 0.8199%
gnomAD_G_SAS: 1.3821%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-193207461-C-T [0/1] rs138751019
Variant score: 0.000
Transcripts:
CDC73:ENST00000367435.5:c.1030+3609C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.6348%
gnomAD_G_AFR: 0.1277%
gnomAD_G_AMR: 0.6739%
gnomAD_G_NFE: 0.7218%
gnomAD_G_SAS: 1.1387%

IFT80

Exomiser Score: 0.217 (p=1.9E-1)

Phenotype Score: 0.531

Variant Score: 0.707

Phenotype matches:
Phenotypic similarity 0.531 to Short rib-polydactyly syndrome, Verma-Naumoff type associated with IFT80.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010306, Short thorax
HP:0006625, Multifocal breast carcinoma - HP:0010306, Short thorax
Phenotypic similarity 0.367 to mouse mutant involving IFT80.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0010099, abnormal thoracic cage shape
HP:0006625, Multifocal breast carcinoma - MP:0010099, abnormal thoracic cage shape
Phenotypic similarity 0.284 to zebrafish mutant involving IFT80.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0000645, chondrocranium morphology, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0000645, chondrocranium morphology, abnormal
Proximity score 0.500 in interactome to LHX4 and phenotypic similarity 0.676 to Combined pituitary hormone deficiencies, genetic forms associated with LHX4.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
HP:0006625, Multifocal breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
Known diseases:
OMIM:611263 Short-rib thoracic dysplasia 2 with or without polydactyly - autosomal recessive
ORPHA:474 Jeune syndrome - autosomal recessive
ORPHA:93271 Short rib-polydactyly syndrome, Verma-Naumoff type - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.217 (p=1.9E-1)

Phenotype Score: 0.531

Variant Score: 0.707

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.531 to ORPHA:93271 Short rib-polydactyly syndrome, Verma-Naumoff type
Phenotypic similarity 0.525 to ORPHA:474 Jeune syndrome
Phenotypic similarity 0.524 to OMIM:611263 Short-rib thoracic dysplasia 2 with or without polydactyly
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-160311726-C-T [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.763 CONTRIBUTING VARIANT
Transcripts:
IFT80:ENST00000326448.12:c.958-3945G>A:p.(=)
Pathogenicity Data:
Best Score: 0.763211
REMM: 0.763
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-160378820-G-C [0/1] rs577604705
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.650 CONTRIBUTING VARIANT
Transcripts:
IFT80:ENST00000326448.12:c.260-1280C>G:p.(=)
Pathogenicity Data:
Best Score: 0.659883
REMM: 0.660
Frequency Data:
gnomAD_G_AMR: 0.0720%
gnomAD_G_NFE: 0.0500%
gnomAD_G_SAS: 0.1040%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.025 (p=3.8E-1)

Phenotype Score: 0.250

Variant Score: 0.763

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-160311726-C-T [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.763 CONTRIBUTING VARIANT
Transcripts:
IFT80:ENST00000326448.12:c.958-3945G>A:p.(=)
Pathogenicity Data:
Best Score: 0.763211
REMM: 0.763
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-160287954-A-G [0/1] rs1305084290
Variant score: 0.645
Transcripts:
IFT80:ENST00000326448.12:c.1316-2086T>C:p.(=)
Pathogenicity Data:
Best Score: 0.647002
REMM: 0.647
Frequency Data:
gnomAD_G_NFE: 0.0044%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT INS 3-160271391-T-TTGAA [0/1] rs1333492335
Variant score: 0.634
Transcripts:
IFT80:ENST00000326448.12:c.2100-2856_2100-2855insTTCA:p.(=)
Pathogenicity Data:
Best Score: 0.63586
REMM: 0.636
Frequency Data:
gnomAD_G_NFE: 0.0044%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 3-160292475-CT-C [0/1] rs142116230
Variant score: 0.215
Transcripts:
IFT80:ENST00000326448.12:c.1316-6608del:p.(=)
Pathogenicity Data:
Best Score: 0.215301
REMM: 0.215
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-160323616-C-A [0/1]
Variant score: 0.084
Transcripts:
IFT80:ENST00000326448.12:c.778-3677G>T:p.(=)
Pathogenicity Data:
Best Score: 0.0840925
REMM: 0.084
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT INS 3-160397716-C-CTTT [0/1] rs545413654
Variant score: 0.018
Transcripts:
IFT80:ENST00000326448.12:c.-47+1429_-47+1430insAAA:p.(=)
Pathogenicity Data:
Best Score: 0.0178655
REMM: 0.018
Frequency Data:
No frequency data

NDOR1

Exomiser Score: 0.215 (p=1.9E-1)

Phenotype Score: 0.508

Variant Score: 0.732

Phenotype matches:
Proximity score 0.508 in interactome to BRIP1 and phenotypic similarity 0.998 to Hereditary breast and/or ovarian cancer syndrome associated with BRIP1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.215 (p=1.9E-1)

Phenotype Score: 0.508

Variant Score: 0.732

No phenotype matches to diseases with this MOI.
Variants contributing to score:
THREE_PRIME_UTR_EXON_VARIANT SNV 9-137218771-C-T [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.732 CONTRIBUTING VARIANT
Transcripts:
NDOR1:ENST00000684003.1:c.*2355C>T:p.(=)
Pathogenicity Data:
Best Score: 0.731534
REMM: 0.732
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.107 (p=2.6E-1)

Phenotype Score: 0.508

Variant Score: 0.641

No phenotype matches to diseases with this MOI.
Variants contributing to score:
THREE_PRIME_UTR_EXON_VARIANT SNV 9-137218771-C-T [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.732 CONTRIBUTING VARIANT
Transcripts:
NDOR1:ENST00000684003.1:c.*2355C>T:p.(=)
Pathogenicity Data:
Best Score: 0.731534
REMM: 0.732
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 9-137215195-C-T [0/1] rs150718423
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.551 CONTRIBUTING VARIANT
Transcripts:
NDOR1:ENST00000684003.1:c.1166C>T:p.(Ser389Leu)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.3042%
gnomAD_E_AFR: 0.0359%
gnomAD_E_AMR: 0.2332%
gnomAD_E_NFE: 0.2969%
gnomAD_E_SAS: 0.4734%
gnomAD_G_AFR: 0.0385%
gnomAD_G_AMR: 0.2743%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.3984%
gnomAD_G_SAS: 0.3935%

PTPRE

Exomiser Score: 0.213 (p=1.9E-1)

Phenotype Score: 0.502

Variant Score: 0.737

Phenotype matches:
Phenotypic similarity 0.300 to mouse mutant involving PTPRE.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0010878, increased trabecular bone volume
HP:0006625, Multifocal breast carcinoma - MP:0010878, increased trabecular bone volume
Proximity score 0.502 in interactome to OPCML and phenotypic similarity 0.998 to Ovarian cancer, somatic associated with OPCML.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.213 (p=1.9E-1)

Phenotype Score: 0.502

Variant Score: 0.737

No phenotype matches to diseases with this MOI.
Variants contributing to score:
FIVE_PRIME_UTR_INTRON_VARIANT DEL 10-127978530-GACCC-G [0|1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.737 CONTRIBUTING VARIANT
Transcripts:
PTPRE:ENST00000254667.8:c.-30-3743_-30-3740del:p.(=)
Pathogenicity Data:
Best Score: 0.736536
REMM: 0.737
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.209 (p=1.9E-1)

Phenotype Score: 0.502

Variant Score: 0.734

No phenotype matches to diseases with this MOI.
Variants contributing to score:
FIVE_PRIME_UTR_INTRON_VARIANT DEL 10-127978530-GACCC-G [0|1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.737 CONTRIBUTING VARIANT
Transcripts:
PTPRE:ENST00000254667.8:c.-30-3743_-30-3740del:p.(=)
Pathogenicity Data:
Best Score: 0.736536
REMM: 0.737
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT INS 10-127968044-G-GTA [1|0] rs1554903040
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.731 CONTRIBUTING VARIANT
Transcripts:
PTPRE:ENST00000254667.8:c.-30-14230_-30-14229insTA:p.(=)
Pathogenicity Data:
Best Score: 0.897948
REMM: 0.898
Frequency Data:
gnomAD_G_AFR: 0.2619%
gnomAD_G_AMR: 0.6212%
gnomAD_G_EAS: 0.0584%
gnomAD_G_NFE: 0.8640%
gnomAD_G_SAS: 0.1686%
Other passed variants:
FIVE_PRIME_UTR_INTRON_VARIANT DEL 10-128034507-TAGTG-T [0/1]
Variant score: 0.724
Transcripts:
PTPRE:ENST00000254667.8:c.-7-6367_-7-6364del:p.(=)
Pathogenicity Data:
Best Score: 0.723785
REMM: 0.724
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT INS 10-127978534-C-CGGGG [0|1]
Variant score: 0.662
Transcripts:
PTPRE:ENST00000254667.8:c.-30-3740_-30-3739insGGGG:p.(=)
Pathogenicity Data:
Best Score: 0.662156
REMM: 0.662
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT DEL 10-128002683-CTTT-C [1/1]
Variant score: 0.596
Transcripts:
PTPRE:ENST00000254667.8:c.-8+20388_-8+20390del:p.(=)
Pathogenicity Data:
Best Score: 0.596424
REMM: 0.596
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT DEL 10-127904174-CTTT-C [0/1]
Variant score: 0.472
Transcripts:
PTPRE:ENST00000254667.8::
Pathogenicity Data:
Best Score: 0.472152
REMM: 0.472
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT INS 10-128024303-C-CTAT [0/1] rs576781633
Variant score: 0.454
Transcripts:
PTPRE:ENST00000254667.8:c.-7-16572_-7-16571insTAT:p.(=)
Pathogenicity Data:
Best Score: 0.561707
REMM: 0.562
Frequency Data:
UK10K: 0.7934%
gnomAD_G_AFR: 0.1708%
gnomAD_G_AMR: 0.2940%
gnomAD_G_NFE: 0.8834%
gnomAD_G_SAS: 0.1864%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-128059445-G-A [0/1] rs77948825
Variant score: 0.403
Transcripts:
PTPRE:ENST00000254667.8:c.512-1494G>A:p.(=)
Pathogenicity Data:
Best Score: 0.544088
REMM: 0.544
Frequency Data:
UK10K: 1.0711%
gnomAD_G_AFR: 0.1972%
gnomAD_G_AMR: 0.1894%
gnomAD_G_NFE: 1.0133%
gnomAD_G_SAS: 0.1449%
DOWNSTREAM_GENE_VARIANT INS 10-128085898-C-CAAAAAA [0/1] rs10691838
Variant score: 0.343
Transcripts:
PTPRE:ENST00000254667.8::
Pathogenicity Data:
Best Score: 0.342792
REMM: 0.343
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 10-128041646-CAA-C [1/1]
Variant score: 0.302
Transcripts:
PTPRE:ENST00000254667.8:c.109+657_109+658del:p.(=)
Pathogenicity Data:
Best Score: 0.30151
REMM: 0.302
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 10-128038090-C-T [0/1] rs963733352
Variant score: 0.070
Transcripts:
PTPRE:ENST00000254667.8:c.-7-2785C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0710766
REMM: 0.071
Frequency Data:
gnomAD_G_EAS: 0.0772%
gnomAD_G_NFE: 0.0029%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 10-128011773-G-T [0/1]
Variant score: 0.033
Transcripts:
PTPRE:ENST00000254667.8:c.-7-29102G>T:p.(=)
Pathogenicity Data:
Best Score: 0.0332373
REMM: 0.033
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 10-127894877-C-T [0/1]
Variant score: 0.000
Transcripts:
PTPRE:ENST00000254667.8::
Pathogenicity Data:
Best Score: 4.11111E-4
REMM: 0.000
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT INS 10-127969682-A-AGG [0|1]
Variant score: 0.000
Transcripts:
PTPRE:ENST00000254667.8:c.-30-12592_-30-12591insGG:p.(=)
Pathogenicity Data:
Best Score: 2.0E-4
REMM: 0.000
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 10-127893929-C-T [0/1] rs11018389
Variant score: 0.000
Transcripts:
PTPRE:ENST00000254667.8::
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.5290%
gnomAD_G_AFR: 0.1083%
gnomAD_G_AMR: 0.3597%
gnomAD_G_NFE: 0.5940%
gnomAD_G_SAS: 0.1035%

DYNC1I1

Exomiser Score: 0.208 (p=1.9E-1)

Phenotype Score: 0.510

Variant Score: 0.724

Phenotype matches:
Proximity score 0.510 in interactome to MC1R and phenotypic similarity 0.950 to Familial melanoma associated with MC1R.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0100013, Neoplasm of the breast
HP:0006625, Multifocal breast carcinoma - HP:0100013, Neoplasm of the breast
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.208 (p=1.9E-1)

Phenotype Score: 0.510

Variant Score: 0.724

No phenotype matches to diseases with this MOI.
Variants contributing to score:
FIVE_PRIME_UTR_INTRON_VARIANT SNV 7-95773353-G-A [0/1] rs189679990
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.755 CONTRIBUTING VARIANT
Transcripts:
DYNC1I1:ENST00000447467.6:c.-10+580G>A:p.(=)
Pathogenicity Data:
Best Score: 0.845129
REMM: 0.845
Frequency Data:
UK10K: 0.2777%
gnomAD_G_AFR: 0.0505%
gnomAD_G_AMR: 0.2288%
gnomAD_G_NFE: 0.2852%
gnomAD_G_SAS: 0.5804%
INTERGENIC_VARIANT INS 7-95767038-G-GA [0/1] rs542148266
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.693 CONTRIBUTING VARIANT
Transcripts:
DYNC1I1:ENST00000447467.6::
Pathogenicity Data:
Best Score: 0.767078
REMM: 0.767
Frequency Data:
gnomAD_G_AFR: 0.0481%
gnomAD_G_AMR: 0.2288%
gnomAD_G_NFE: 0.2869%
gnomAD_G_SAS: 0.5396%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.078 (p=2.9E-1)

Phenotype Score: 0.510

Variant Score: 0.600

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 7-96080399-G-A [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.600 CONTRIBUTING VARIANT
Transcripts:
DYNC1I1:ENST00000447467.6:c.1687G>A:p.(Ala563Thr)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_NFE: 0.0002%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-95922981-A-C [0/1] rs533144326
Variant score: 0.463
Transcripts:
DYNC1I1:ENST00000447467.6:c.490+52983A>C:p.(=)
Pathogenicity Data:
Best Score: 0.487322
REMM: 0.487
Frequency Data:
UK10K: 0.0264%
gnomAD_G_AFR: 0.0120%
gnomAD_G_AMR: 0.0131%
gnomAD_G_NFE: 0.0397%
gnomAD_G_SAS: 0.3113%
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-95936956-T-TCTCACACACACACACACA [0/1] rs750834189
Variant score: 0.395
Transcripts:
DYNC1I1:ENST00000447467.6:c.491-40556_491-40555insCTCACACACACACACACA:p.(=)
Pathogenicity Data:
Best Score: 0.395074
REMM: 0.395
Frequency Data:
No frequency data
INTERGENIC_VARIANT INS 7-96113547-A-AT [0/1] rs71127442
Variant score: 0.389
Transcripts:
DYNC1I1:ENST00000447467.6::
Pathogenicity Data:
Best Score: 0.389108
REMM: 0.389
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 7-96117676-CAAAAAAAAAAAAAAAAAAAAA-C [0/1]
Variant score: 0.383
Transcripts:
DYNC1I1:ENST00000447467.6::
Pathogenicity Data:
Best Score: 0.382617
REMM: 0.383
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 7-95776062-C-T [0/1] rs1386280971
Variant score: 0.349
Transcripts:
DYNC1I1:ENST00000447467.6:c.-10+3289C>T:p.(=)
Pathogenicity Data:
Best Score: 0.349677
REMM: 0.350
Frequency Data:
gnomAD_G_AFR: 0.0048%
gnomAD_G_NFE: 0.0029%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-95913652-T-C [0/1] rs140624584
Variant score: 0.262
Transcripts:
DYNC1I1:ENST00000447467.6:c.490+43654T>C:p.(=)
Pathogenicity Data:
Best Score: 0.453914
REMM: 0.454
Frequency Data:
UK10K: 1.4150%
gnomAD_G_AFR: 0.2886%
gnomAD_G_AMR: 0.7130%
gnomAD_G_EAS: 0.0579%
gnomAD_G_NFE: 1.1922%
gnomAD_G_SAS: 0.7460%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-96041660-C-T [0/1] rs148747693
Variant score: 0.241
Transcripts:
DYNC1I1:ENST00000447467.6:c.1509+2239C>T:p.(=)
Pathogenicity Data:
Best Score: 0.401571
REMM: 0.402
Frequency Data:
UK10K: 1.0976%
gnomAD_G_AFR: 1.1822%
gnomAD_G_AMR: 1.2570%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.3768%
gnomAD_G_SAS: 0.2490%
INTERGENIC_VARIANT SNV 7-96108668-C-T [0/1] rs192541650
Variant score: 0.180
Transcripts:
DYNC1I1:ENST00000447467.6::
Pathogenicity Data:
Best Score: 0.192503
REMM: 0.193
Frequency Data:
gnomAD_G_AFR: 0.0603%
gnomAD_G_AMR: 0.2951%
gnomAD_G_NFE: 0.3841%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-96014566-G-T [0/1] rs1794358126
Variant score: 0.123
Transcripts:
DYNC1I1:ENST00000447467.6:c.970-13609G>T:p.(=)
Pathogenicity Data:
Best Score: 0.122892
REMM: 0.123
Frequency Data:
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-95880640-CTT-C [1/1] rs142182653
Variant score: 0.088
Transcripts:
DYNC1I1:ENST00000447467.6:c.490+10643_490+10644del:p.(=)
Pathogenicity Data:
Best Score: 0.0883361
REMM: 0.088
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-95944979-T-A [0/1] rs769701651
Variant score: 0.079
Transcripts:
DYNC1I1:ENST00000447467.6:c.491-32533T>A:p.(=)
Pathogenicity Data:
Best Score: 0.0787488
REMM: 0.079
Frequency Data:
gnomAD_G_NFE: 0.0015%
gnomAD_G_SAS: 0.0208%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-95833779-G-A [0|1] rs10953163
Variant score: 0.063
Transcripts:
DYNC1I1:ENST00000447467.6:c.374+5663G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0627496
REMM: 0.063
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 7-95757292-G-A [0/1] rs57774137
Variant score: 0.062
Transcripts:
DYNC1I1:ENST00000447467.6::
Pathogenicity Data:
Best Score: 0.089671
REMM: 0.090
Frequency Data:
gnomAD_G_AFR: 0.4528%
gnomAD_G_AMR: 0.0650%
gnomAD_G_EAS: 1.1990%
gnomAD_G_NFE: 0.1730%
gnomAD_G_SAS: 0.0727%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-96076740-A-G [0/1] rs569154681
Variant score: 0.060
Transcripts:
DYNC1I1:ENST00000447467.6:c.1650+543A>G:p.(=)
Pathogenicity Data:
Best Score: 0.061173
REMM: 0.061
Frequency Data:
gnomAD_G_AMR: 0.0131%
gnomAD_G_NFE: 0.0147%
gnomAD_G_SAS: 0.1242%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-95909243-TGG-T [0/1]
Variant score: 0.054
Transcripts:
DYNC1I1:ENST00000447467.6:c.490+39246_490+39247del:p.(=)
Pathogenicity Data:
Best Score: 0.0539492
REMM: 0.054
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-96074550-CAAAAA-C [0/1] rs61571160
Variant score: 0.051
Transcripts:
DYNC1I1:ENST00000447467.6:c.1510-1506_1510-1502del:p.(=)
Pathogenicity Data:
Best Score: 0.0576056
REMM: 0.058
Frequency Data:
gnomAD_G_AFR: 0.0673%
gnomAD_G_AMR: 0.4494%
gnomAD_G_NFE: 0.5952%
gnomAD_G_SAS: 0.1792%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-95909243-TG-T [0/1]
Variant score: 0.044
Transcripts:
DYNC1I1:ENST00000447467.6:c.490+39246del:p.(=)
Pathogenicity Data:
Best Score: 0.0439849
REMM: 0.044
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-95834757-G-A [0/1] rs199867306
Variant score: 0.029
Transcripts:
DYNC1I1:ENST00000447467.6:c.374+6641G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0292433
REMM: 0.029
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-95835151-C-T [0|1] rs13235093
Variant score: 0.016
Transcripts:
DYNC1I1:ENST00000447467.6:c.374+7035C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0164845
REMM: 0.016
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 7-95800817-G-A [0/1] rs569225688
Variant score: 0.009
Transcripts:
DYNC1I1:ENST00000447467.6:c.-9-3904G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0144103
REMM: 0.014
Frequency Data:
UK10K: 0.2645%
gnomAD_G_AFR: 0.0505%
gnomAD_G_AMR: 0.2875%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.3219%
gnomAD_G_SAS: 1.3049%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-95835155-C-G [0|1] rs13235098
Variant score: 0.002
Transcripts:
DYNC1I1:ENST00000447467.6:c.374+7039C>G:p.(=)
Pathogenicity Data:
Best Score: 0.00211111
REMM: 0.002
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-95972712-C-T [0/1] rs1037077890
Variant score: 0.001
Transcripts:
DYNC1I1:ENST00000447467.6:c.491-4800C>T:p.(=)
Pathogenicity Data:
Best Score: 6.0E-4
REMM: 0.001
Frequency Data:
gnomAD_G_AFR: 0.0097%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-95943560-T-C [1/1] rs199998890
Variant score: 0.001
Transcripts:
DYNC1I1:ENST00000447467.6:c.491-33952T>C:p.(=)
Pathogenicity Data:
Best Score: 5.33333E-4
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-95944879-T-G [1/1] rs56016882
Variant score: 0.001
Transcripts:
DYNC1I1:ENST00000447467.6:c.491-32633T>G:p.(=)
Pathogenicity Data:
Best Score: 5.0E-4
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-95817214-T-TA [0/1] rs34412998
Variant score: 0.000
Transcripts:
DYNC1I1:ENST00000447467.6:c.314+3877_314+3878insA:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0635%
gnomAD_G_AMR: 0.0361%
gnomAD_G_EAS: 0.0412%
gnomAD_G_NFE: 0.0679%
gnomAD_G_SAS: 0.5249%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-95832214-T-C [0|1] rs1227509
Variant score: 0.000
Transcripts:
DYNC1I1:ENST00000447467.6:c.374+4098T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-95834454-C-A [0/1] rs78434435
Variant score: 0.000
Transcripts:
DYNC1I1:ENST00000447467.6:c.374+6338C>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-95943007-G-T [1/1] rs9691452
Variant score: 0.000
Transcripts:
DYNC1I1:ENST00000447467.6:c.491-34505G>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-95943018-A-G [1/1] rs200240862
Variant score: 0.000
Transcripts:
DYNC1I1:ENST00000447467.6:c.491-34494A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-95970810-C-T [0/1] rs572128043
Variant score: 0.000
Transcripts:
DYNC1I1:ENST00000447467.6:c.491-6702C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.2513%
gnomAD_G_AFR: 0.0530%
gnomAD_G_AMR: 0.3010%
gnomAD_G_EAS: 0.0386%
gnomAD_G_NFE: 0.2823%
gnomAD_G_SAS: 1.4102%

EGF

Exomiser Score: 0.208 (p=1.9E-1)

Phenotype Score: 0.502

Variant Score: 0.733

Phenotype matches:
Phenotypic similarity 0.222 to zebrafish mutant involving EGF.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0001067, ceratobranchial cartilage aplastic, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0001067, ceratobranchial cartilage aplastic, abnormal
Proximity score 0.502 in interactome to TERT and phenotypic similarity 0.950 to Familial melanoma associated with TERT.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0100013, Neoplasm of the breast
HP:0006625, Multifocal breast carcinoma - HP:0100013, Neoplasm of the breast
Proximity score 0.502 in interactome to TERT and phenotypic similarity 0.357 to mouse mutant of TERT.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0003345, decreased rib number
HP:0006625, Multifocal breast carcinoma - MP:0003345, decreased rib number
Known diseases:
OMIM:611718 ?Hypomagnesemia 4, renal (unconfirmed)
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.208 (p=1.9E-1)

Phenotype Score: 0.502

Variant Score: 0.733

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-109914557-C-G [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.755 CONTRIBUTING VARIANT
Transcripts:
EGF:ENST00000265171.10:c.127+1095C>G:p.(=)
Pathogenicity Data:
Best Score: 0.754591
REMM: 0.755
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-109966835-G-A [0/1] rs377058282
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.710 CONTRIBUTING VARIANT
Transcripts:
EGF:ENST00000265171.10:c.1576-2136G>A:p.(=)
Pathogenicity Data:
Best Score: 0.726576
REMM: 0.727
Frequency Data:
UK10K: 0.1322%
gnomAD_G_AFR: 0.0217%
gnomAD_G_AMR: 0.0916%
gnomAD_G_NFE: 0.1516%
gnomAD_G_SAS: 0.0416%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.023 (p=3.9E-1)

Phenotype Score: 0.251

Variant Score: 0.755

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-109914557-C-G [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.755 CONTRIBUTING VARIANT
Transcripts:
EGF:ENST00000265171.10:c.127+1095C>G:p.(=)
Pathogenicity Data:
Best Score: 0.754591
REMM: 0.755
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-109925925-G-C [0/1]
Variant score: 0.556
Transcripts:
EGF:ENST00000265171.10:c.127+12463G>C:p.(=)
Pathogenicity Data:
Best Score: 0.556126
REMM: 0.556
Frequency Data:
No frequency data
SYNONYMOUS_VARIANT SNV 4-109968997-G-A [0/1] rs140682556
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:1, LB:2, B:1)
Variant score: 0.095
Transcripts:
EGF:ENST00000265171.10:c.1602G>A:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.2116%
gnomAD_E_AFR: 0.0508%
gnomAD_E_AMR: 0.1431%
gnomAD_E_NFE: 0.3021%
gnomAD_E_SAS: 0.0267%
gnomAD_G_AFR: 0.0505%
gnomAD_G_AMR: 0.1570%
gnomAD_G_NFE: 0.3058%
INTERGENIC_VARIANT SNV 4-109899718-G-A [0/1]
Variant score: 0.083
Transcripts:
EGF:ENST00000265171.10::
Pathogenicity Data:
Best Score: 0.0825988
REMM: 0.083
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-109992963-G-A [1/1] rs11569069
Variant score: 0.067
Transcripts:
EGF:ENST00000265171.10:c.2735-284G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0671385
REMM: 0.067
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 4-109893428-G-T [0/1] rs114231843
Variant score: 0.000
Transcripts:
EGF:ENST00000265171.10::
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.2298%
gnomAD_G_AFR: 0.1757%
gnomAD_G_AMR: 0.6157%
gnomAD_G_NFE: 1.4374%
gnomAD_G_SAS: 0.2697%
CODING_TRANSCRIPT_INTRON_VARIANT INS 4-109932360-C-CATATATATATATATATATATATATATATAT [1/1] rs57424246
Variant score: 0.000
Transcripts:
EGF:ENST00000265171.10:c.128-8586_128-8585insATATATATATATATATATATATATATATAT:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.2929%
gnomAD_G_AMR: 0.4857%
gnomAD_G_EAS: 0.5471%
gnomAD_G_NFE: 0.7187%
gnomAD_G_SAS: 0.5188%

TBP

Exomiser Score: 0.205 (p=2.0E-1)

Phenotype Score: 0.504

Variant Score: 0.729

Phenotype matches:
Proximity score 0.504 in interactome to NF1 and phenotypic similarity 0.946 to 17q11 microdeletion syndrome associated with NF1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.504 in interactome to NF1 and phenotypic similarity 0.604 to mouse mutant of NF1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0001267, enlarged chest
HP:0006625, Multifocal breast carcinoma - MP:0001267, enlarged chest
Known diseases:
OMIM:168600 Parkinson disease, susceptibility to (susceptibility)
OMIM:607136 Spinocerebellar ataxia 17 - autosomal dominant
ORPHA:98759 Spinocerebellar ataxia type 17 - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.205 (p=2.0E-1)

Phenotype Score: 0.504

Variant Score: 0.729

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-170566820-T-C [0/1] rs565127661
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.729 CONTRIBUTING VARIANT
Transcripts:
TBP:ENST00000392092.7:c.586-98T>C:p.(=)
Pathogenicity Data:
Best Score: 0.729909
REMM: 0.730
Frequency Data:
gnomAD_E_AMR: 0.0029%
gnomAD_E_NFE: 0.0026%
gnomAD_G_NFE: 0.0073%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.001 (p=7.3E-1)

Phenotype Score: 0.252

Variant Score: 0.405

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-170566820-T-C [0/1] rs565127661
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.729 CONTRIBUTING VARIANT
Transcripts:
TBP:ENST00000392092.7:c.586-98T>C:p.(=)
Pathogenicity Data:
Best Score: 0.729909
REMM: 0.730
Frequency Data:
gnomAD_E_AMR: 0.0029%
gnomAD_E_NFE: 0.0026%
gnomAD_G_NFE: 0.0073%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-170568815-CT-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.080 CONTRIBUTING VARIANT
Transcripts:
TBP:ENST00000392092.7:c.678-796del:p.(=)
Pathogenicity Data:
Best Score: 0.0802849
REMM: 0.080
Frequency Data:
No frequency data

LEP

Exomiser Score: 0.204 (p=2.0E-1)

Phenotype Score: 0.614

Variant Score: 0.605

Phenotype matches:
Phenotypic similarity 0.614 to Obesity due to congenital leptin deficiency associated with LEP.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Phenotypic similarity 0.326 to mouse mutant involving LEP.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0005605, increased bone mass
HP:0006625, Multifocal breast carcinoma - MP:0005605, increased bone mass
Proximity score 0.519 in interactome to NHLH2 and phenotypic similarity 0.616 to Normosmic congenital hypogonadotropic hypogonadism associated with NHLH2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003187, Breast hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0003187, Breast hypoplasia
Proximity score 0.519 in interactome to NHLH2 and phenotypic similarity 0.328 to mouse mutant of NHLH2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0003795, abnormal bone structure
HP:0006625, Multifocal breast carcinoma - MP:0003795, abnormal bone structure
Known diseases:
OMIM:614962 Obesity, morbid, due to leptin deficiency - autosomal recessive
ORPHA:66628 Obesity due to congenital leptin deficiency - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.204 (p=2.0E-1)

Phenotype Score: 0.614

Variant Score: 0.605

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.614 to ORPHA:66628 Obesity due to congenital leptin deficiency
Phenotypic similarity 0.614 to OMIM:614962 Obesity, morbid, due to leptin deficiency
Variants contributing to score:
THREE_PRIME_UTR_EXON_VARIANT SNV 7-128256512-T-C [0/1] rs1483827030
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PP4]
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.742 CONTRIBUTING VARIANT
Transcripts:
LEP:ENST00000308868.5:c.*1749T>C:p.(=)
Pathogenicity Data:
Best Score: 0.743981
REMM: 0.744
Frequency Data:
gnomAD_G_AMR: 0.0065%
gnomAD_G_NFE: 0.0029%
gnomAD_G_SAS: 0.0207%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 7-128248329-G-A [0/1] rs369973417
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PP4]
Variant score: 0.467 CONTRIBUTING VARIANT
Transcripts:
LEP:ENST00000308868.5:c.-28-3662G>A:p.(=)
Pathogenicity Data:
Best Score: 0.626286
REMM: 0.626
Frequency Data:
UK10K: 0.0661%
gnomAD_G_AFR: 0.0072%
gnomAD_G_AMR: 0.0849%
gnomAD_G_NFE: 0.0867%
gnomAD_G_SAS: 1.0563%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.022 (p=3.9E-1)

Phenotype Score: 0.259

Variant Score: 0.742

No phenotype matches to diseases with this MOI.
Variants contributing to score:
THREE_PRIME_UTR_EXON_VARIANT SNV 7-128256512-T-C [0/1] rs1483827030
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.742 CONTRIBUTING VARIANT
Transcripts:
LEP:ENST00000308868.5:c.*1749T>C:p.(=)
Pathogenicity Data:
Best Score: 0.743981
REMM: 0.744
Frequency Data:
gnomAD_G_AMR: 0.0065%
gnomAD_G_NFE: 0.0029%
gnomAD_G_SAS: 0.0207%
Other passed variants:
INTERGENIC_VARIANT DEL 7-128228534-ATTTT-A [1/1] rs60674057
Variant score: 0.559
Transcripts:
LEP:ENST00000308868.5::
Pathogenicity Data:
Best Score: 0.558804
REMM: 0.559
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 7-128277129-C-T [0/1]
Variant score: 0.063
Transcripts:
LEP:ENST00000308868.5::
Pathogenicity Data:
Best Score: 0.0625758
REMM: 0.063
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 7-128223997-C-G [0/1] rs374671590
Variant score: 0.000
Transcripts:
LEP:ENST00000308868.5::
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.0793%
gnomAD_G_AFR: 0.0073%
gnomAD_G_AMR: 0.0915%
gnomAD_G_NFE: 0.0985%
gnomAD_G_SAS: 1.0149%

GLI2

Exomiser Score: 0.202 (p=2.0E-1)

Phenotype Score: 0.676

Variant Score: 0.532

Phenotype matches:
Phenotypic similarity 0.676 to Combined pituitary hormone deficiencies, genetic forms associated with GLI2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
HP:0006625, Multifocal breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
Phenotypic similarity 0.336 to mouse mutant involving GLI2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0004174, abnormal spine curvature
HP:0006625, Multifocal breast carcinoma - MP:0004174, abnormal spine curvature
Phenotypic similarity 0.280 to zebrafish mutant involving GLI2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0000645, chondrocranium morphology, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0000645, chondrocranium morphology, abnormal
Proximity score 0.502 in interactome to PRKCD and phenotypic similarity 0.876 to Autoimmune lymphoproliferative syndrome associated with PRKCD.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010619, Fibroadenoma of the breast
HP:0006625, Multifocal breast carcinoma - HP:0010619, Fibroadenoma of the breast
Proximity score 0.502 in interactome to PRKCD and phenotypic similarity 0.302 to mouse mutant of PRKCD.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0008395, abnormal osteoblast differentiation
HP:0006625, Multifocal breast carcinoma - MP:0008395, abnormal osteoblast differentiation
Known diseases:
OMIM:610829 Holoprosencephaly 9 - autosomal dominant
OMIM:615849 Culler-Jones syndrome - autosomal dominant
ORPHA:220386 Semilobar holoprosencephaly - autosomal dominant
ORPHA:280195 Septopreoptic holoprosencephaly - autosomal dominant
ORPHA:280200 Microform holoprosencephaly - autosomal dominant
ORPHA:93924 Lobar holoprosencephaly - autosomal dominant
ORPHA:93925 Alobar holoprosencephaly - autosomal dominant
ORPHA:93926 Midline interhemispheric variant of holoprosencephaly - autosomal dominant
ORPHA:95494 Combined pituitary hormone deficiencies, genetic forms - autosomal dominant/recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.202 (p=2.0E-1)

Phenotype Score: 0.676

Variant Score: 0.532

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.676 to ORPHA:95494 Combined pituitary hormone deficiencies, genetic forms
Variants contributing to score:
INTERGENIC_VARIANT SNV 2-121006954-C-T [0/1] rs114709036
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PP4]
Variant score: 0.588 CONTRIBUTING VARIANT
Transcripts:
GLI2:ENST00000361492.9::
Pathogenicity Data:
Best Score: 0.713045
REMM: 0.713
Frequency Data:
UK10K: 0.7934%
gnomAD_G_AFR: 0.1156%
gnomAD_G_AMR: 0.3269%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 0.8144%
gnomAD_G_SAS: 0.8313%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-120892434-A-G [0|1] rs138193772
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PP4]
Variant score: 0.476 CONTRIBUTING VARIANT
Transcripts:
GLI2:ENST00000361492.9:c.149-34927A>G:p.(=)
Pathogenicity Data:
Best Score: 0.583127
REMM: 0.583
Frequency Data:
UK10K: 0.8596%
gnomAD_G_AFR: 0.1660%
gnomAD_G_AMR: 0.8496%
gnomAD_G_NFE: 0.8555%
gnomAD_G_SAS: 0.1863%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.014 (p=4.3E-1)

Phenotype Score: 0.676

Variant Score: 0.221

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.676 to ORPHA:95494 Combined pituitary hormone deficiencies, genetic forms
Phenotypic similarity 0.471 to ORPHA:280195 Septopreoptic holoprosencephaly
Variants contributing to score:
FIVE_PRIME_UTR_INTRON_VARIANT INS 2-120753093-A-AT [0/1] rs55697602
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting, PP4]
Variant score: 0.221 CONTRIBUTING VARIANT
Transcripts:
GLI2:ENST00000361492.9:c.-31+16808_-31+16809insT:p.(=)
Pathogenicity Data:
Best Score: 0.220862
REMM: 0.221
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 2-120923278-GTACAACACACACATACACAGCAATGCATATGTACACA-G [1/1] rs757767732
Variant score: 0.438
Transcripts:
GLI2:ENST00000361492.9:c.149-4082_149-4046del:p.(=)
Pathogenicity Data:
Best Score: 0.438461
REMM: 0.438
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 2-120989968-A-G [0/1] rs149140724
ClinVar: BENIGN_OR_LIKELY_BENIGN (CRITERIA_PROVIDED_MULTIPLE_SUBMITTERS_NO_CONFLICTS)
Variant score: 0.246
Transcripts:
GLI2:ENST00000361492.9:c.4003A>G:p.(Met1335Val)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 1.6794%
gnomAD_E_AFR: 0.2332%
gnomAD_E_AMR: 0.3702%
gnomAD_E_NFE: 1.4796%
gnomAD_E_SAS: 0.5330%
gnomAD_G_AFR: 0.2646%
gnomAD_G_AMR: 0.6662%
gnomAD_G_NFE: 1.4562%
gnomAD_G_SAS: 0.5807%
MISSENSE_VARIANT SNV 2-120990472-G-A [0/1] rs114814747
ClinVar: BENIGN_OR_LIKELY_BENIGN (CRITERIA_PROVIDED_MULTIPLE_SUBMITTERS_NO_CONFLICTS)
Variant score: 0.246
Transcripts:
GLI2:ENST00000361492.9:c.4507G>A:p.(Asp1503Asn)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 1.6794%
gnomAD_E_AFR: 0.2360%
gnomAD_E_AMR: 0.3645%
gnomAD_E_EAS: 0.0025%
gnomAD_E_NFE: 1.4643%
gnomAD_E_SAS: 1.1675%
gnomAD_G_AFR: 0.2629%
gnomAD_G_AMR: 0.6549%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 1.4398%
gnomAD_G_SAS: 0.9607%
INTERGENIC_VARIANT DEL 2-120725479-CT-C [0/1] rs138941990
Variant score: 0.233
Transcripts:
GLI2:ENST00000361492.9::
Pathogenicity Data:
Best Score: 0.240645
REMM: 0.241
Frequency Data:
gnomAD_G_AFR: 0.2184%
gnomAD_G_AMR: 0.0334%
gnomAD_G_EAS: 0.0588%
gnomAD_G_NFE: 0.0119%
INTERGENIC_VARIANT SNV 2-121003562-G-T [0/1] rs115970536
Variant score: 0.218
Transcripts:
GLI2:ENST00000361492.9::
Pathogenicity Data:
Best Score: 0.263386
REMM: 0.263
Frequency Data:
UK10K: 0.8199%
gnomAD_G_AFR: 0.1203%
gnomAD_G_AMR: 0.3265%
gnomAD_G_NFE: 0.8216%
gnomAD_G_SAS: 0.4353%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-120832192-C-A [0/1] rs146566400
Variant score: 0.186
Transcripts:
GLI2:ENST00000361492.9:c.148+34724C>A:p.(=)
Pathogenicity Data:
Best Score: 0.724719
REMM: 0.725
Frequency Data:
UK10K: 1.8381%
gnomAD_G_AFR: 0.3007%
gnomAD_G_AMR: 1.1757%
gnomAD_G_EAS: 0.1353%
gnomAD_G_NFE: 1.8711%
gnomAD_G_SAS: 1.4487%
INTERGENIC_VARIANT INS 2-120723720-A-ATATTATATAATATATAT [1|1] rs1558768345
Variant score: 0.065
Transcripts:
GLI2:ENST00000361492.9::
Pathogenicity Data:
Best Score: 0.0704452
REMM: 0.070
Frequency Data:
gnomAD_G_AFR: 0.2326%
gnomAD_G_EAS: 0.4505%
gnomAD_G_NFE: 0.4711%
gnomAD_G_SAS: 0.1773%
INTERGENIC_VARIANT INS 2-120723786-T-TTATATATATATTATATATATATTATATAA [0|1] rs71412751
Variant score: 0.059
Transcripts:
GLI2:ENST00000361492.9::
Pathogenicity Data:
Best Score: 0.0639103
REMM: 0.064
Frequency Data:
gnomAD_G_AFR: 0.3296%
gnomAD_G_NFE: 0.1395%
gnomAD_G_SAS: 0.4762%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 2-120881760-AC-A [0|1]
Variant score: 0.047
Transcripts:
GLI2:ENST00000361492.9:c.149-45600del:p.(=)
Pathogenicity Data:
Best Score: 0.046906
REMM: 0.047
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-120881754-A-G [0|1]
Variant score: 0.040
Transcripts:
GLI2:ENST00000361492.9:c.149-45607A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0399385
REMM: 0.040
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT SNV 2-120735039-T-A [0/1]
Variant score: 0.008
Transcripts:
GLI2:ENST00000361492.9::
Pathogenicity Data:
Best Score: 0.00835119
REMM: 0.008
Frequency Data:
No frequency data
THREE_PRIME_UTR_EXON_VARIANT INS 2-120992050-A-ACACACCC [0/1] rs1553480327
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.002
Transcripts:
GLI2:ENST00000361492.9:c.*1376_*1377insACACCCC:p.(=)
Pathogenicity Data:
Best Score: 0.0024
REMM: 0.002
Frequency Data:
gnomAD_G_AFR: 0.0471%
gnomAD_G_AMR: 0.0749%
gnomAD_G_NFE: 0.2002%
gnomAD_G_SAS: 0.1772%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-120803894-G-C [0/1] rs566960984
Variant score: 0.001
Transcripts:
GLI2:ENST00000361492.9:c.148+6426G>C:p.(=)
Pathogenicity Data:
Best Score: 0.001
REMM: 0.001
Frequency Data:
gnomAD_G_AFR: 0.0145%
gnomAD_G_AMR: 0.0327%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.0029%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-120840285-G-A [0/1] rs903954304
Variant score: 0.000
Transcripts:
GLI2:ENST00000361492.9:c.148+42817G>A:p.(=)
Pathogenicity Data:
Best Score: 2.0E-4
REMM: 0.000
Frequency Data:
gnomAD_G_AMR: 0.0066%
gnomAD_G_EAS: 0.0386%
gnomAD_G_NFE: 0.0132%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-120883516-G-T [0/1] rs947495087
Variant score: 0.000
Transcripts:
GLI2:ENST00000361492.9:c.149-43845G>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AMR: 0.0065%
gnomAD_G_NFE: 0.0132%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-120909860-G-A [0/1] rs184424477
Variant score: 0.000
Transcripts:
GLI2:ENST00000361492.9:c.149-17501G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.2116%
gnomAD_G_AFR: 0.0361%
gnomAD_G_AMR: 0.1111%
gnomAD_G_EAS: 0.1733%
gnomAD_G_NFE: 0.3043%
gnomAD_G_SAS: 0.0414%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-120922038-C-G [0/1] rs1013682984
Variant score: 0.000
Transcripts:
GLI2:ENST00000361492.9:c.149-5323C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_SAS: 0.0207%

LAMA2

Exomiser Score: 0.195 (p=2.0E-1)

Phenotype Score: 0.502

Variant Score: 0.725

Phenotype matches:
Phenotypic similarity 0.408 to Laminin subunit alpha 2-related congenital muscular dystrophy associated with LAMA2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0004878, Intercostal muscle weakness
HP:0006625, Multifocal breast carcinoma - HP:0004878, Intercostal muscle weakness
Phenotypic similarity 0.368 to mouse mutant involving LAMA2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000161, scoliosis
HP:0006625, Multifocal breast carcinoma - MP:0000161, scoliosis
Proximity score 0.502 in interactome to ITGA3 and phenotypic similarity 0.603 to Epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome associated with ITGA3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Known diseases:
OMIM:607855 Muscular dystrophy, congenital, merosin deficient or partially deficient - autosomal recessive
OMIM:618138 Muscular dystrophy, limb-girdle, autosomal recessive 23 - autosomal recessive
ORPHA:258 Laminin subunit alpha 2-related congenital muscular dystrophy - autosomal recessive
ORPHA:258 Laminin subunit alpha 2-related congenital muscular dystrophy - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.195 (p=2.0E-1)

Phenotype Score: 0.502

Variant Score: 0.725

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.408 to ORPHA:258 Laminin subunit alpha 2-related congenital muscular dystrophy
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129032771-G-A [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.818 CONTRIBUTING VARIANT
Transcripts:
LAMA2:ENST00000421865.3:c.113-17147G>A:p.(=)
Pathogenicity Data:
Best Score: 0.818452
REMM: 0.818
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129487858-G-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.631 CONTRIBUTING VARIANT
Transcripts:
LAMA2:ENST00000421865.3:c.7898+1236G>C:p.(=)
Pathogenicity Data:
Best Score: 0.630661
REMM: 0.631
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.041 (p=3.4E-1)

Phenotype Score: 0.251

Variant Score: 0.818

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129032771-G-A [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.818 CONTRIBUTING VARIANT
Transcripts:
LAMA2:ENST00000421865.3:c.113-17147G>A:p.(=)
Pathogenicity Data:
Best Score: 0.818452
REMM: 0.818
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129114077-A-G [0/1] rs368356753
Variant score: 0.594
Transcripts:
LAMA2:ENST00000421865.3:c.639+15662A>G:p.(=)
Pathogenicity Data:
Best Score: 0.620835
REMM: 0.621
Frequency Data:
UK10K: 0.2777%
gnomAD_G_AFR: 0.0241%
gnomAD_G_AMR: 0.0787%
gnomAD_G_NFE: 0.2002%
gnomAD_G_SAS: 0.0621%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129005415-C-T [0/1] rs188976405
Variant score: 0.572
Transcripts:
LAMA2:ENST00000421865.3:c.113-44503C>T:p.(=)
Pathogenicity Data:
Best Score: 0.603014
REMM: 0.603
Frequency Data:
UK10K: 0.0793%
gnomAD_G_AFR: 0.0434%
gnomAD_G_AMR: 0.3211%
gnomAD_G_NFE: 0.1722%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129392847-T-C [0/1]
Variant score: 0.569
Transcripts:
LAMA2:ENST00000421865.3:c.5235-198T>C:p.(=)
Pathogenicity Data:
Best Score: 0.569466
REMM: 0.569
Frequency Data:
No frequency data
DOWNSTREAM_GENE_VARIANT DEL 6-129520373-TAAAAAAAAAAAA-T [0/1] rs574588197
Variant score: 0.545
Transcripts:
LAMA2:ENST00000421865.3::
Pathogenicity Data:
Best Score: 0.544775
REMM: 0.545
Frequency Data:
No frequency data
DOWNSTREAM_GENE_VARIANT DEL 6-129520373-TAAAAAAAAAAAAA-T [0/1] rs574588197
Variant score: 0.545
Transcripts:
LAMA2:ENST00000421865.3::
Pathogenicity Data:
Best Score: 0.544775
REMM: 0.545
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129120071-G-T [0/1]
Variant score: 0.545
Transcripts:
LAMA2:ENST00000421865.3:c.639+21656G>T:p.(=)
Pathogenicity Data:
Best Score: 0.544565
REMM: 0.545
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129078000-T-C [0/1]
Variant score: 0.538
Transcripts:
LAMA2:ENST00000421865.3:c.396+18104T>C:p.(=)
Pathogenicity Data:
Best Score: 0.538313
REMM: 0.538
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-128901198-A-G [0/1]
Variant score: 0.467
Transcripts:
LAMA2:ENST00000421865.3:c.112+17841A>G:p.(=)
Pathogenicity Data:
Best Score: 0.466896
REMM: 0.467
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT DEL 6-128879572-TA-T [0|1] rs1435978801
Variant score: 0.350
Transcripts:
LAMA2:ENST00000421865.3::
Pathogenicity Data:
Best Score: 0.51121
REMM: 0.511
Frequency Data:
gnomAD_G_AFR: 0.1731%
gnomAD_G_AMR: 0.6534%
gnomAD_G_NFE: 1.2027%
gnomAD_G_SAS: 0.0668%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-129396965-CAATGAGA-C [0|1]
Variant score: 0.301
Transcripts:
LAMA2:ENST00000421865.3:c.5445+3711_5445+3717del:p.(=)
Pathogenicity Data:
Best Score: 0.30082
REMM: 0.301
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT INS 6-128879570-T-TGCC [0|1] rs1361436889
Variant score: 0.281
Transcripts:
LAMA2:ENST00000421865.3::
Pathogenicity Data:
Best Score: 0.414729
REMM: 0.415
Frequency Data:
gnomAD_G_AFR: 0.1756%
gnomAD_G_AMR: 0.6455%
gnomAD_G_NFE: 1.2185%
gnomAD_G_SAS: 0.0688%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-129012335-AG-A [0/1] rs372706983
Variant score: 0.276
Transcripts:
LAMA2:ENST00000421865.3:c.113-37582del:p.(=)
Pathogenicity Data:
Best Score: 0.448208
REMM: 0.448
Frequency Data:
UK10K: 1.0976%
gnomAD_G_AFR: 0.2334%
gnomAD_G_AMR: 0.7515%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.3457%
gnomAD_G_SAS: 0.2070%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-128920700-T-C [0/1] rs188129086
Variant score: 0.210
Transcripts:
LAMA2:ENST00000421865.3:c.112+37343T>C:p.(=)
Pathogenicity Data:
Best Score: 0.224906
REMM: 0.225
Frequency Data:
UK10K: 0.0397%
gnomAD_G_AFR: 0.0579%
gnomAD_G_AMR: 0.4007%
gnomAD_G_EAS: 0.0387%
gnomAD_G_NFE: 0.2296%
gnomAD_G_SAS: 0.0622%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-129286881-TA-T [1/1] rs376556325
Variant score: 0.207
Transcripts:
LAMA2:ENST00000421865.3:c.2538-965del:p.(=)
Pathogenicity Data:
Best Score: 0.206886
REMM: 0.207
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129286883-A-T [1/1] rs796581646
Variant score: 0.207
Transcripts:
LAMA2:ENST00000421865.3:c.2538-964A>T:p.(=)
Pathogenicity Data:
Best Score: 0.206886
REMM: 0.207
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-129286688-TTATATAATA-T [0/1] rs376311435
Variant score: 0.205
Transcripts:
LAMA2:ENST00000421865.3:c.2538-1158_2538-1150del:p.(=)
Pathogenicity Data:
Best Score: 0.207646
REMM: 0.208
Frequency Data:
gnomAD_G_NFE: 0.1053%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-129286614-TTATATAATA-T [0/1] rs1477714196
Variant score: 0.152
Transcripts:
LAMA2:ENST00000421865.3:c.2538-1232_2538-1224del:p.(=)
Pathogenicity Data:
Best Score: 0.152026
REMM: 0.152
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-129286931-T-TTCTTATTTATATAAATA [0/1]
Variant score: 0.130
Transcripts:
LAMA2:ENST00000421865.3:c.2538-916_2538-915insTCTTATTTATATAAATA:p.(=)
Pathogenicity Data:
Best Score: 0.130325
REMM: 0.130
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129088087-C-G [1|1] rs12198534
Variant score: 0.116
Transcripts:
LAMA2:ENST00000421865.3:c.397-10086C>G:p.(=)
Pathogenicity Data:
Best Score: 0.117644
REMM: 0.118
Frequency Data:
gnomAD_G_AFR: 0.1069%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129088079-C-T [1|1] rs12198530
Variant score: 0.115
Transcripts:
LAMA2:ENST00000421865.3:c.397-10094C>T:p.(=)
Pathogenicity Data:
Best Score: 0.118672
REMM: 0.119
Frequency Data:
gnomAD_G_AFR: 0.2261%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-129396973-CAGTGAGA-C [0|1]
Variant score: 0.114
Transcripts:
LAMA2:ENST00000421865.3:c.5445+3719_5445+3725del:p.(=)
Pathogenicity Data:
Best Score: 0.114211
REMM: 0.114
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129088088-C-G [1|1] rs7450865
Variant score: 0.112
Transcripts:
LAMA2:ENST00000421865.3:c.397-10085C>G:p.(=)
Pathogenicity Data:
Best Score: 0.115477
REMM: 0.115
Frequency Data:
gnomAD_G_AFR: 0.1032%
gnomAD_G_SAS: 0.2075%
SYNONYMOUS_VARIANT SNV 6-129050060-C-T [0/1] rs142083777
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:2, LB:3)
Variant score: 0.095
Transcripts:
LAMA2:ENST00000421865.3:c.255C>T:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.0793%
gnomAD_E_AFR: 0.0149%
gnomAD_E_AMR: 0.0559%
gnomAD_E_NFE: 0.1223%
gnomAD_E_SAS: 0.0058%
gnomAD_G_AFR: 0.0433%
gnomAD_G_AMR: 0.3007%
gnomAD_G_NFE: 0.1544%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-129286852-T-TTTATATAA [1/1]
Variant score: 0.078
Transcripts:
LAMA2:ENST00000421865.3:c.2538-995_2538-994insTTATATAA:p.(=)
Pathogenicity Data:
Best Score: 0.0778135
REMM: 0.078
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129286853-A-T [1/1] rs866482943
Variant score: 0.078
Transcripts:
LAMA2:ENST00000421865.3:c.2538-994A>T:p.(=)
Pathogenicity Data:
Best Score: 0.0778135
REMM: 0.078
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129003772-T-C [0/1] rs113980912
Variant score: 0.076
Transcripts:
LAMA2:ENST00000421865.3:c.113-46146T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0764202
REMM: 0.076
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129003907-A-G [0|1]
Variant score: 0.073
Transcripts:
LAMA2:ENST00000421865.3:c.113-46011A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0733433
REMM: 0.073
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129003916-T-G [0|1]
Variant score: 0.073
Transcripts:
LAMA2:ENST00000421865.3:c.113-46002T>G:p.(=)
Pathogenicity Data:
Best Score: 0.0733433
REMM: 0.073
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129003919-G-C [0|1]
Variant score: 0.073
Transcripts:
LAMA2:ENST00000421865.3:c.113-45999G>C:p.(=)
Pathogenicity Data:
Best Score: 0.0733433
REMM: 0.073
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-128998621-C-CA [1/1] rs11425031
Variant score: 0.072
Transcripts:
LAMA2:ENST00000421865.3:c.113-51297_113-51296insA:p.(=)
Pathogenicity Data:
Best Score: 0.0715075
REMM: 0.072
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129003697-T-A [0/1] rs199566018
Variant score: 0.071
Transcripts:
LAMA2:ENST00000421865.3:c.113-46221T>A:p.(=)
Pathogenicity Data:
Best Score: 0.0705798
REMM: 0.071
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-129396981-CAG-C [0|1]
Variant score: 0.059
Transcripts:
LAMA2:ENST00000421865.3:c.5445+3727_5445+3728del:p.(=)
Pathogenicity Data:
Best Score: 0.0587968
REMM: 0.059
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-128998670-G-A [0/1]
Variant score: 0.053
Transcripts:
LAMA2:ENST00000421865.3:c.113-51248G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0534024
REMM: 0.053
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT DEL 6-128879487-ATATATATATGCCAT-A [0|1] rs1477864290
Variant score: 0.047
Transcripts:
LAMA2:ENST00000421865.3::
Pathogenicity Data:
Best Score: 0.0714742
REMM: 0.071
Frequency Data:
gnomAD_G_AFR: 0.2226%
gnomAD_G_AMR: 0.5776%
gnomAD_G_NFE: 1.2467%
gnomAD_G_SAS: 0.0686%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129003274-C-T [1/1] rs1196991415
Variant score: 0.043
Transcripts:
LAMA2:ENST00000421865.3:c.113-46644C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0434405
REMM: 0.043
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129223261-G-C [0/1] rs185852861
Variant score: 0.043
Transcripts:
LAMA2:ENST00000421865.3:c.1783-26851G>C:p.(=)
Pathogenicity Data:
Best Score: 0.0438917
REMM: 0.044
Frequency Data:
gnomAD_G_AFR: 0.0144%
gnomAD_G_AMR: 0.0915%
gnomAD_G_NFE: 0.0588%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129003183-A-G [0/1] rs28799311
Variant score: 0.041
Transcripts:
LAMA2:ENST00000421865.3:c.113-46735A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0413905
REMM: 0.041
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 6-128868665-CAAAAAAA-C [1/1]
Variant score: 0.039
Transcripts:
LAMA2:ENST00000421865.3::
Pathogenicity Data:
Best Score: 0.0391556
REMM: 0.039
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129499176-A-G [0/1] rs185429741
Variant score: 0.039
Transcripts:
LAMA2:ENST00000421865.3:c.8245-3483A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0405742
REMM: 0.041
Frequency Data:
UK10K: 0.1587%
gnomAD_G_AFR: 0.0482%
gnomAD_G_AMR: 0.0785%
gnomAD_G_NFE: 0.2368%
gnomAD_G_SAS: 0.2285%
INTERGENIC_VARIANT DEL 6-129527306-CTT-C [0/1] rs564729607
Variant score: 0.034
Transcripts:
LAMA2:ENST00000421865.3::
Pathogenicity Data:
Best Score: 0.0340032
REMM: 0.034
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-129251076-CTA-C [0/1] rs71714357
Variant score: 0.032
Transcripts:
LAMA2:ENST00000421865.3:c.1884+864_1884+865del:p.(=)
Pathogenicity Data:
Best Score: 0.0322766
REMM: 0.032
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-129251076-CTATA-C [0/1] rs71714357
Variant score: 0.032
Transcripts:
LAMA2:ENST00000421865.3:c.1884+864_1884+867del:p.(=)
Pathogenicity Data:
Best Score: 0.0322766
REMM: 0.032
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-128999034-T-C [1/1] rs201642979
Variant score: 0.032
Transcripts:
LAMA2:ENST00000421865.3:c.113-50884T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0320849
REMM: 0.032
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-129066039-T-TATGTC [0/1]
Variant score: 0.023
Transcripts:
LAMA2:ENST00000421865.3:c.396+6143_396+6144insATGTC:p.(=)
Pathogenicity Data:
Best Score: 0.0230536
REMM: 0.023
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-129066047-T-TTTTTTTTTTTTTTC [0/1]
Variant score: 0.023
Transcripts:
LAMA2:ENST00000421865.3:c.396+6151_396+6152insTTTTTTTTTTTTTC:p.(=)
Pathogenicity Data:
Best Score: 0.0230536
REMM: 0.023
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-129066038-G-GTATGTCTTTTTTTTTTTTTTTTTTTTTTTT [0/1] rs59543848
Variant score: 0.023
Transcripts:
LAMA2:ENST00000421865.3:c.396+6142_396+6143insTATGTCTTTTTTTTTTTTTTTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.0230536
REMM: 0.023
Frequency Data:
gnomAD_G_AFR: 0.0171%
gnomAD_G_NFE: 0.0203%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-129271464-CT-C [1/1] rs11287525
Variant score: 0.021
Transcripts:
LAMA2:ENST00000421865.3:c.2450+714del:p.(=)
Pathogenicity Data:
Best Score: 0.0210956
REMM: 0.021
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129002873-A-C [1/1]
Variant score: 0.020
Transcripts:
LAMA2:ENST00000421865.3:c.113-47045A>C:p.(=)
Pathogenicity Data:
Best Score: 0.0202008
REMM: 0.020
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT DEL 6-128879525-ATATATATGCCAT-A [0|1] rs1314498775
Variant score: 0.017
Transcripts:
LAMA2:ENST00000421865.3::
Pathogenicity Data:
Best Score: 0.0369964
REMM: 0.037
Frequency Data:
gnomAD_G_AFR: 0.2727%
gnomAD_G_AMR: 0.6951%
gnomAD_G_NFE: 1.6037%
gnomAD_G_SAS: 0.1134%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129000447-A-G [1/1]
Variant score: 0.016
Transcripts:
LAMA2:ENST00000421865.3:c.113-49471A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0159187
REMM: 0.016
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129000316-G-A [1/1] rs201135219
Variant score: 0.012
Transcripts:
LAMA2:ENST00000421865.3:c.113-49602G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0122881
REMM: 0.012
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-129398472-C-CT [1/1] rs71028159
Variant score: 0.008
Transcripts:
LAMA2:ENST00000421865.3:c.5446-2752_5446-2751insT:p.(=)
Pathogenicity Data:
Best Score: 0.00815833
REMM: 0.008
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129251082-A-C [0/1]
Variant score: 0.007
Transcripts:
LAMA2:ENST00000421865.3:c.1884+869A>C:p.(=)
Pathogenicity Data:
Best Score: 0.0074
REMM: 0.007
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129468039-T-G [0/1] rs886067842
Variant score: 0.007
Transcripts:
LAMA2:ENST00000421865.3:c.7300+2750T>G:p.(=)
Pathogenicity Data:
Best Score: 0.0073
REMM: 0.007
Frequency Data:
gnomAD_G_AFR: 0.0024%
gnomAD_G_NFE: 0.0044%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-128999559-T-A [0/1] rs200113382
Variant score: 0.007
Transcripts:
LAMA2:ENST00000421865.3:c.113-50359T>A:p.(=)
Pathogenicity Data:
Best Score: 0.00651548
REMM: 0.007
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129049778-G-A [0/1] rs138352398
Variant score: 0.006
Transcripts:
LAMA2:ENST00000421865.3:c.113-140G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00658333
REMM: 0.007
Frequency Data:
UK10K: 0.1058%
gnomAD_E_AFR: 0.0188%
gnomAD_E_AMR: 0.1836%
gnomAD_E_NFE: 0.1829%
gnomAD_E_SAS: 0.0741%
gnomAD_G_AFR: 0.0457%
gnomAD_G_AMR: 0.3596%
gnomAD_G_NFE: 0.2338%
gnomAD_G_SAS: 0.0829%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129356506-G-A [0/1] rs531375682
Variant score: 0.006
Transcripts:
LAMA2:ENST00000421865.3:c.4717+3149G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00613651
REMM: 0.006
Frequency Data:
UK10K: 0.0926%
gnomAD_G_AFR: 0.0145%
gnomAD_G_AMR: 0.1702%
gnomAD_G_NFE: 0.1663%
gnomAD_G_SAS: 0.0415%
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-129298091-G-GGTTGTGTCCCTCCCTGTCTGTGACTTTGATTCAGCCAGTCACTCAAACACTGCTACTCAGTAAAAATCAGCAGATGCTCT [0|1]
Variant score: 0.002
Transcripts:
LAMA2:ENST00000421865.3:c.3037+226_3037+227insGTTGTGTCCCTCCCTGTCTGTGACTTTGATTCAGCCAGTCACTCAAACACTGCTACTCAGTAAAAATCAGCAGATGCTCT:p.(=)
Pathogenicity Data:
Best Score: 0.00215
REMM: 0.002
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-129298090-C-CTTTT [0|1] rs1295582829
ClinVar: BENIGN (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.001
Transcripts:
LAMA2:ENST00000421865.3:c.3037+225_3037+226insTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.0013
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129380772-C-T [0/1] rs191645452
Variant score: 0.001
Transcripts:
LAMA2:ENST00000421865.3:c.4960-2350C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0012
REMM: 0.001
Frequency Data:
UK10K: 0.0793%
gnomAD_G_AFR: 0.0144%
gnomAD_G_AMR: 0.1243%
gnomAD_G_NFE: 0.1426%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129067477-G-A [0/1] rs149522749
Variant score: 0.001
Transcripts:
LAMA2:ENST00000421865.3:c.396+7581G>A:p.(=)
Pathogenicity Data:
Best Score: 0.001
REMM: 0.001
Frequency Data:
UK10K: 1.2431%
gnomAD_G_AFR: 0.2383%
gnomAD_G_AMR: 0.7585%
gnomAD_G_NFE: 1.3574%
gnomAD_G_SAS: 0.1866%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129020080-C-T [0/1] rs184937552
Variant score: 0.000
Transcripts:
LAMA2:ENST00000421865.3:c.113-29838C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0444%
gnomAD_G_AMR: 0.4032%
gnomAD_G_NFE: 0.2384%
gnomAD_G_SAS: 0.0920%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129051627-T-C [0|1] rs540226668
Variant score: 0.000
Transcripts:
LAMA2:ENST00000421865.3:c.283+1539T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_NFE: 0.0059%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129219735-A-C [1|1] rs265349
Variant score: 0.000
Transcripts:
LAMA2:ENST00000421865.3:c.1782+26882A>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129219744-A-G [1|1] rs265348
Variant score: 0.000
Transcripts:
LAMA2:ENST00000421865.3:c.1782+26891A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129251080-A-C [0/1]
Variant score: 0.000
Transcripts:
LAMA2:ENST00000421865.3:c.1884+867A>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-129385156-G-A [1/1] rs111642361
Variant score: 0.000
Transcripts:
LAMA2:ENST00000421865.3:c.5071+1923G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.5285%
gnomAD_G_NFE: 0.6438%

TNFAIP3

Exomiser Score: 0.194 (p=2.0E-1)

Phenotype Score: 0.502

Variant Score: 0.724

Phenotype matches:
Phenotypic similarity 0.256 to mouse mutant involving TNFAIP3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002933, joint inflammation
HP:0006625, Multifocal breast carcinoma - MP:0002933, joint inflammation
Phenotypic similarity 0.252 to zebrafish mutant involving TNFAIP3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0002682, pharyngeal arch cartilage malformed, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0002682, pharyngeal arch cartilage malformed, abnormal
Proximity score 0.502 in interactome to IKBKG and phenotypic similarity 0.619 to Incontinentia pigmenti associated with IKBKG.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0100783, Breast aplasia
HP:0006625, Multifocal breast carcinoma - HP:0100783, Breast aplasia
Proximity score 0.502 in interactome to IKBKG and phenotypic similarity 0.275 to mouse mutant of IKBKG.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002398, abnormal bone marrow cell morphology/development
HP:0006625, Multifocal breast carcinoma - MP:0002398, abnormal bone marrow cell morphology/development
Known diseases:
OMIM:616744 Autoinflammatory syndrome, familial, Behcet-like 1 - autosomal dominant
ORPHA:536 Systemic lupus erythematosus (susceptibility)
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.194 (p=2.0E-1)

Phenotype Score: 0.502

Variant Score: 0.724

No phenotype matches to diseases with this MOI.
Variants contributing to score:
UPSTREAM_GENE_VARIANT INS 6-137864336-C-CAAAAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.724 CONTRIBUTING VARIANT
Transcripts:
TNFAIP3:ENST00000612899.5::
Pathogenicity Data:
Best Score: 0.723939
REMM: 0.724
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.017 (p=4.1E-1)

Phenotype Score: 0.251

Variant Score: 0.724

No phenotype matches to diseases with this MOI.
Variants contributing to score:
UPSTREAM_GENE_VARIANT INS 6-137864336-C-CAAAAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.724 CONTRIBUTING VARIANT
Transcripts:
TNFAIP3:ENST00000612899.5::
Pathogenicity Data:
Best Score: 0.723939
REMM: 0.724
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT INS 6-137864336-C-CAAAAAAAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.724 CONTRIBUTING VARIANT
Transcripts:
TNFAIP3:ENST00000612899.5::
Pathogenicity Data:
Best Score: 0.723939
REMM: 0.724
Frequency Data:
No frequency data
Other passed variants:
MISSENSE_VARIANT SNV 6-137880103-A-C [0/1] rs142253225
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:2, LB:1, B:1)
Variant score: 0.548
Transcripts:
TNFAIP3:ENST00000612899.5:c.1939A>C:p.(Thr647Pro)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.1719%
gnomAD_E_AFR: 0.0448%
gnomAD_E_AMR: 0.2817%
gnomAD_E_EAS: 0.0050%
gnomAD_E_NFE: 0.2094%
gnomAD_E_SAS: 0.0684%
gnomAD_G_AFR: 0.0601%
gnomAD_G_AMR: 0.4972%
gnomAD_G_NFE: 0.2205%
gnomAD_G_SAS: 0.0621%
INTERGENIC_VARIANT INS 6-137896731-C-CAAAAAAAAAAAAAAAAAAAAAA [0/1] rs10552462
Variant score: 0.384
Transcripts:
TNFAIP3:ENST00000612899.5::
Pathogenicity Data:
Best Score: 0.39049
REMM: 0.390
Frequency Data:
gnomAD_G_AFR: 0.0147%
gnomAD_G_AMR: 0.1229%
gnomAD_G_NFE: 0.0249%
INTERGENIC_VARIANT SNV 6-137858370-C-T [0/1] rs1582875052
Variant score: 0.000
Transcripts:
TNFAIP3:ENST00000612899.5::
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0024%

IGF1

Exomiser Score: 0.186 (p=2.1E-1)

Phenotype Score: 0.504

Variant Score: 0.715

Phenotype matches:
Phenotypic similarity 0.320 to mouse mutant involving IGF1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0005508, abnormal skeleton morphology
HP:0006625, Multifocal breast carcinoma - MP:0005508, abnormal skeleton morphology
Proximity score 0.504 in interactome to TWIST1 and phenotypic similarity 0.998 to Saethre-Chotzen syndrome with or without eyelid anomalies associated with TWIST1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.504 in interactome to TWIST1 and phenotypic similarity 0.356 to mouse mutant of TWIST1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000137, abnormal vertebrae morphology
HP:0006625, Multifocal breast carcinoma - MP:0000137, abnormal vertebrae morphology
Proximity score 0.504 in interactome to TWIST1 and phenotypic similarity 0.257 to fish mutant of TWIST1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0007632, notochord absent, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0007632, notochord absent, abnormal
Known diseases:
OMIM:608747 Insulin-like growth factor I deficiency - autosomal recessive
ORPHA:73272 Growth delay due to insulin-like growth factor type 1 deficiency - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.186 (p=2.1E-1)

Phenotype Score: 0.504

Variant Score: 0.715

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-102478639-C-G [0/1] rs573200814
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.943 CONTRIBUTING VARIANT
Transcripts:
IGF1:ENST00000337514.11:c.63+1680G>C:p.(=)
Pathogenicity Data:
Best Score: 0.980214
REMM: 0.980
Frequency Data:
UK10K: 0.0132%
gnomAD_E_AFR: 0.0034%
gnomAD_E_AMR: 0.0728%
gnomAD_E_NFE: 0.0342%
gnomAD_E_SAS: 0.1924%
gnomAD_G_AFR: 0.0096%
gnomAD_G_AMR: 0.0262%
gnomAD_G_NFE: 0.0382%
gnomAD_G_SAS: 0.2488%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-102403623-ATTT-A [0/1] rs142169670
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.488 CONTRIBUTING VARIANT
Transcripts:
IGF1:ENST00000337514.11:c.403-1060_403-1058del:p.(=)
Pathogenicity Data:
Best Score: 0.487913
REMM: 0.488
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.002 (p=6.4E-1)

Phenotype Score: 0.252

Variant Score: 0.488

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-102403623-ATTT-A [0/1] rs142169670
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.488 CONTRIBUTING VARIANT
Transcripts:
IGF1:ENST00000337514.11:c.403-1060_403-1058del:p.(=)
Pathogenicity Data:
Best Score: 0.487913
REMM: 0.488
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-102407094-CAAAAAAAAAAAAAAAAAAAA-C [0/1]
Variant score: 0.417
Transcripts:
IGF1:ENST00000337514.11:c.403-4548_403-4529del:p.(=)
Pathogenicity Data:
Best Score: 0.416935
REMM: 0.417
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-102415543-TTTCC-T [0/1] rs761981548
Variant score: 0.396
Transcripts:
IGF1:ENST00000337514.11:c.402+3962_402+3965del:p.(=)
Pathogenicity Data:
Best Score: 0.396358
REMM: 0.396
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-102415543-T-TTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCGTCCTTCCTTCC [0/1] rs1555239065
Variant score: 0.263
Transcripts:
IGF1:ENST00000337514.11:c.402+3965_402+3966insGGAAGGAAGGACGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAA:p.(=)
Pathogenicity Data:
Best Score: 0.263312
REMM: 0.263
Frequency Data:
No frequency data
THREE_PRIME_UTR_EXON_VARIANT INS 12-102402245-T-TA [0/1] rs1555236089
Variant score: 0.196
Transcripts:
IGF1:ENST00000337514.11:c.*261_*262insT:p.(=)
Pathogenicity Data:
Best Score: 0.415308
REMM: 0.415
Frequency Data:
gnomAD_E_AFR: 0.1722%
gnomAD_E_AMR: 0.2726%
gnomAD_E_EAS: 0.1803%
gnomAD_E_NFE: 0.3398%
gnomAD_E_SAS: 0.0660%
gnomAD_G_AFR: 1.5914%
gnomAD_G_AMR: 0.3036%
gnomAD_G_EAS: 0.2973%
gnomAD_G_NFE: 0.7146%
gnomAD_G_SAS: 0.1953%
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-102428236-G-GTATATATATATATATATATATATATATATATATATATATA [0/1]
Variant score: 0.124
Transcripts:
IGF1:ENST00000337514.11:c.221-8547_221-8546insTATATATATATATATATATATATATATATATATATATATA:p.(=)
Pathogenicity Data:
Best Score: 0.124256
REMM: 0.124
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-102452261-C-CAA [0/1]
Variant score: 0.035
Transcripts:
IGF1:ENST00000337514.11:c.220+23381_220+23382insTT:p.(=)
Pathogenicity Data:
Best Score: 0.0348762
REMM: 0.035
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-102458635-TG-T [0/1] rs566862763
Variant score: 0.020
Transcripts:
IGF1:ENST00000337514.11:c.220+17007del:p.(=)
Pathogenicity Data:
Best Score: 0.021056
REMM: 0.021
Frequency Data:
UK10K: 0.0264%
gnomAD_G_AFR: 0.0103%
gnomAD_G_AMR: 0.0307%
gnomAD_G_NFE: 0.0416%
gnomAD_G_SAS: 0.4250%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-102406751-A-G [0/1] rs549090655
Variant score: 0.009
Transcripts:
IGF1:ENST00000337514.11:c.403-4185T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0140937
REMM: 0.014
Frequency Data:
UK10K: 0.0264%
gnomAD_G_AFR: 0.0120%
gnomAD_G_AMR: 0.0327%
gnomAD_G_NFE: 0.0456%
gnomAD_G_SAS: 1.3485%
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-102407094-C-CAAAAAAA [0/1] rs57468885
Variant score: 0.001
Transcripts:
IGF1:ENST00000337514.11:c.403-4529_403-4528insTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 8.11111E-4
REMM: 0.001
Frequency Data:
gnomAD_G_AFR: 0.0394%
gnomAD_G_NFE: 0.0736%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-102453776-A-C [0/1] rs535792134
Variant score: 0.001
Transcripts:
IGF1:ENST00000337514.11:c.220+21867T>G:p.(=)
Pathogenicity Data:
Best Score: 7.5E-4
REMM: 0.001
Frequency Data:
UK10K: 0.0397%
gnomAD_G_AFR: 0.0096%
gnomAD_G_AMR: 0.0261%
gnomAD_G_NFE: 0.0456%
gnomAD_G_SAS: 0.3937%

BMPR1B

Exomiser Score: 0.185 (p=2.1E-1)

Phenotype Score: 0.573

Variant Score: 0.637

Phenotype matches:
Phenotypic similarity 0.329 to mouse mutant involving BMPR1B.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0003795, abnormal bone structure
HP:0006625, Multifocal breast carcinoma - MP:0003795, abnormal bone structure
Proximity score 0.573 in interactome to BMP15 and phenotypic similarity 0.676 to 46,XX gonadal dysgenesis associated with BMP15.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
HP:0006625, Multifocal breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
Known diseases:
OMIM:112600 Brachydactyly, type A2 - autosomal dominant
OMIM:609441 Acromesomelic dysplasia 3 - autosomal recessive
OMIM:616849 Brachydactyly, type A1, D - autosomal dominant
ORPHA:2098 Acromesomelic dysplasia, Grebe type - autosomal recessive
ORPHA:2639 Fibular aplasia-complex brachydactyly syndrome - autosomal recessive
ORPHA:93384 Brachydactyly type C - autosomal dominant/recessive
ORPHA:93388 Brachydactyly type A1 - autosomal dominant
ORPHA:93396 Brachydactyly type A2 - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.185 (p=2.1E-1)

Phenotype Score: 0.573

Variant Score: 0.637

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-95141984-C-T [0/1] rs1056943196
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.637 CONTRIBUTING VARIANT
Transcripts:
BMPR1B:ENST00000515059.6:c.1077-6764C>T:p.(=)
Pathogenicity Data:
Best Score: 0.638225
REMM: 0.638
Frequency Data:
gnomAD_G_AMR: 0.0065%
gnomAD_G_NFE: 0.0132%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.183 (p=2.1E-1)

Phenotype Score: 0.573

Variant Score: 0.636

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-95141984-C-T [0/1] rs1056943196
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.637 CONTRIBUTING VARIANT
Transcripts:
BMPR1B:ENST00000515059.6:c.1077-6764C>T:p.(=)
Pathogenicity Data:
Best Score: 0.638225
REMM: 0.638
Frequency Data:
gnomAD_G_AMR: 0.0065%
gnomAD_G_NFE: 0.0132%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-95057229-A-G [0/1] rs190906996
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.634 CONTRIBUTING VARIANT
Transcripts:
BMPR1B:ENST00000515059.6:c.-17-47179A>G:p.(=)
Pathogenicity Data:
Best Score: 0.727228
REMM: 0.727
Frequency Data:
UK10K: 0.2116%
gnomAD_G_AFR: 0.0530%
gnomAD_G_AMR: 0.3012%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 0.2691%
gnomAD_G_SAS: 0.6650%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-95119222-T-C [0/1]
Variant score: 0.538
Transcripts:
BMPR1B:ENST00000515059.6:c.349+3435T>C:p.(=)
Pathogenicity Data:
Best Score: 0.537858
REMM: 0.538
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94850630-C-T [0/1] rs572175330
Variant score: 0.474
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-25201C>T:p.(=)
Pathogenicity Data:
Best Score: 0.50243
REMM: 0.502
Frequency Data:
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0196%
gnomAD_G_NFE: 0.0279%
gnomAD_G_SAS: 0.3530%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-95077684-C-T [0/1] rs1728816986
Variant score: 0.461
Transcripts:
BMPR1B:ENST00000515059.6:c.-17-26724C>T:p.(=)
Pathogenicity Data:
Best Score: 0.461046
REMM: 0.461
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT INS 4-94841278-T-TG [0/1] rs552443087
Variant score: 0.460
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-34553_-182-34552insG:p.(=)
Pathogenicity Data:
Best Score: 0.460456
REMM: 0.460
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 4-95120610-T-TTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCC [0/1]
Variant score: 0.446
Transcripts:
BMPR1B:ENST00000515059.6:c.350-3200_350-3199insTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCC:p.(=)
Pathogenicity Data:
Best Score: 0.446422
REMM: 0.446
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT DEL 4-95049419-GTTTTTTTTTTTTTTTTTTTTTTTT-G [0/1]
Variant score: 0.428
Transcripts:
BMPR1B:ENST00000515059.6:c.-18+53286_-18+53309del:p.(=)
Pathogenicity Data:
Best Score: 0.42809
REMM: 0.428
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT DEL 4-94957333-GT-G [0/1] rs56341742
Variant score: 0.363
Transcripts:
BMPR1B:ENST00000515059.6:c.-112-38706del:p.(=)
Pathogenicity Data:
Best Score: 0.36317
REMM: 0.363
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT DEL 4-94902081-GT-G [0|1] rs879359255
Variant score: 0.257
Transcripts:
BMPR1B:ENST00000515059.6:c.-113+26182del:p.(=)
Pathogenicity Data:
Best Score: 0.511027
REMM: 0.511
Frequency Data:
gnomAD_G_AFR: 0.2410%
gnomAD_G_AMR: 1.4234%
gnomAD_G_NFE: 1.5416%
gnomAD_G_SAS: 0.3513%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 4-95130723-CTT-C [1/1] rs148720302
Variant score: 0.247
Transcripts:
BMPR1B:ENST00000515059.6:c.779-491_779-490del:p.(=)
Pathogenicity Data:
Best Score: 0.24684
REMM: 0.247
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT DEL 4-94902083-GTGT-G [0|1] rs879910391
Variant score: 0.240
Transcripts:
BMPR1B:ENST00000515059.6:c.-113+26184_-113+26186del:p.(=)
Pathogenicity Data:
Best Score: 0.489416
REMM: 0.489
Frequency Data:
gnomAD_G_AFR: 0.2476%
gnomAD_G_AMR: 1.4098%
gnomAD_G_NFE: 1.5608%
gnomAD_G_SAS: 0.3621%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94841305-T-A [0/1] rs1279783237
Variant score: 0.193
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-34526T>A:p.(=)
Pathogenicity Data:
Best Score: 0.192683
REMM: 0.193
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 4-95150454-GAAA-G [0/1] rs67483429
Variant score: 0.184
Transcripts:
BMPR1B:ENST00000515059.6:c.1252+1532_1252+1534del:p.(=)
Pathogenicity Data:
Best Score: 0.227605
REMM: 0.228
Frequency Data:
gnomAD_G_AFR: 0.0610%
gnomAD_G_AMR: 0.3867%
gnomAD_G_EAS: 0.1214%
gnomAD_G_NFE: 0.3342%
gnomAD_G_SAS: 0.8877%
FIVE_PRIME_UTR_INTRON_VARIANT INS 4-94981005-A-ACGCGCGCG [0/1] rs34635740
Variant score: 0.162
Transcripts:
BMPR1B:ENST00000515059.6:c.-112-15035_-112-15034insCGCGCGCG:p.(=)
Pathogenicity Data:
Best Score: 0.161811
REMM: 0.162
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT SNV 4-94757885-A-C [0/1] rs1174895958
Variant score: 0.162
Transcripts:
BMPR1B:ENST00000515059.6::
Pathogenicity Data:
Best Score: 0.772012
REMM: 0.772
Frequency Data:
gnomAD_E_SAS: 1.9231%
gnomAD_G_AMR: 0.0549%
gnomAD_G_EAS: 0.1333%
gnomAD_G_NFE: 0.0732%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-95042136-G-A [0/1] rs11723059
Variant score: 0.126
Transcripts:
BMPR1B:ENST00000515059.6:c.-18+46002G>A:p.(=)
Pathogenicity Data:
Best Score: 0.147521
REMM: 0.148
Frequency Data:
gnomAD_G_AFR: 0.0553%
gnomAD_G_AMR: 0.3007%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.2749%
gnomAD_G_SAS: 0.7258%
FIVE_PRIME_UTR_INTRON_VARIANT INS 4-94981005-A-ATGCGCGCG [0/1] rs1553923782
Variant score: 0.122
Transcripts:
BMPR1B:ENST00000515059.6:c.-112-15035_-112-15034insTGCGCGCG:p.(=)
Pathogenicity Data:
Best Score: 0.161811
REMM: 0.162
Frequency Data:
gnomAD_G_AFR: 1.0334%
gnomAD_G_AMR: 0.4562%
gnomAD_G_EAS: 0.0794%
gnomAD_G_NFE: 0.3326%
gnomAD_G_SAS: 0.8557%
FIVE_PRIME_UTR_INTRON_VARIANT DEL 4-94840470-CT-C [0/1] rs1467384410
Variant score: 0.116
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-35360del:p.(=)
Pathogenicity Data:
Best Score: 0.115576
REMM: 0.116
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94795134-G-C [1/1] rs149233715
Variant score: 0.113
Transcripts:
BMPR1B:ENST00000515059.6:c.-183+37066G>C:p.(=)
Pathogenicity Data:
Best Score: 0.113354
REMM: 0.113
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94794159-G-A [0/1] rs1355623992
Variant score: 0.106
Transcripts:
BMPR1B:ENST00000515059.6:c.-183+36091G>A:p.(=)
Pathogenicity Data:
Best Score: 0.106138
REMM: 0.106
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94840188-C-G [0/1] rs28807369
Variant score: 0.102
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-35643C>G:p.(=)
Pathogenicity Data:
Best Score: 0.101808
REMM: 0.102
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT INS 4-94770182-G-GTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT [0/1] rs1215939344
Variant score: 0.089
Transcripts:
BMPR1B:ENST00000515059.6:c.-183+12114_-183+12115insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.0896099
REMM: 0.090
Frequency Data:
gnomAD_G_AFR: 0.0521%
gnomAD_G_NFE: 0.0584%
FIVE_PRIME_UTR_INTRON_VARIANT INS 4-95026107-T-TTTCC [0/1] rs1206670464
Variant score: 0.076
Transcripts:
BMPR1B:ENST00000515059.6:c.-18+29973_-18+29974insTTCC:p.(=)
Pathogenicity Data:
Best Score: 0.11614
REMM: 0.116
Frequency Data:
gnomAD_G_AFR: 1.0577%
gnomAD_G_AMR: 0.8219%
gnomAD_G_EAS: 0.6536%
gnomAD_G_NFE: 1.0897%
gnomAD_G_SAS: 1.2662%
FIVE_PRIME_UTR_INTRON_VARIANT INS 4-94840321-T-TG [0/1] rs201880778
Variant score: 0.073
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-35510_-182-35509insG:p.(=)
Pathogenicity Data:
Best Score: 0.0734349
REMM: 0.073
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT INS 4-95026098-A-ATTTCTTTCTTTCTTTCTTTC [0/1]
Variant score: 0.072
Transcripts:
BMPR1B:ENST00000515059.6:c.-18+29964_-18+29965insTTTCTTTCTTTCTTTCTTTC:p.(=)
Pathogenicity Data:
Best Score: 0.0718448
REMM: 0.072
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94839014-T-G [0/1] rs1276437435
Variant score: 0.070
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-36817T>G:p.(=)
Pathogenicity Data:
Best Score: 0.0702317
REMM: 0.070
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94839306-G-A [0|1] rs796155459
Variant score: 0.067
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-36525G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0705516
REMM: 0.071
Frequency Data:
gnomAD_G_AFR: 0.3019%
gnomAD_G_AMR: 0.2729%
gnomAD_G_EAS: 0.0197%
gnomAD_G_NFE: 0.3304%
gnomAD_G_SAS: 0.2084%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94838436-C-A [0/1]
Variant score: 0.064
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-37395C>A:p.(=)
Pathogenicity Data:
Best Score: 0.0637234
REMM: 0.064
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94838882-C-G [0|1]
Variant score: 0.055
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-36949C>G:p.(=)
Pathogenicity Data:
Best Score: 0.054881
REMM: 0.055
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT DEL 4-94780682-CTT-C [0/1] rs869117575
Variant score: 0.050
Transcripts:
BMPR1B:ENST00000515059.6:c.-183+22615_-183+22616del:p.(=)
Pathogenicity Data:
Best Score: 0.0500329
REMM: 0.050
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94839332-G-A [0|1] rs1191498059
Variant score: 0.050
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-36499G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0536544
REMM: 0.054
Frequency Data:
gnomAD_G_AFR: 0.2652%
gnomAD_G_AMR: 0.3156%
gnomAD_G_NFE: 0.2763%
gnomAD_G_SAS: 0.4206%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94839331-C-G [0|1] rs1446858100
Variant score: 0.048
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-36500C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0518544
REMM: 0.052
Frequency Data:
gnomAD_G_AFR: 0.2573%
gnomAD_G_AMR: 0.3028%
gnomAD_G_NFE: 0.2796%
gnomAD_G_SAS: 0.4248%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94841048-A-G [0/1] rs545029923
Variant score: 0.043
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-34783A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0480151
REMM: 0.048
Frequency Data:
gnomAD_G_AFR: 0.3773%
gnomAD_G_AMR: 0.5674%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 0.2386%
gnomAD_G_SAS: 0.4460%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94838889-G-T [0|1]
Variant score: 0.043
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-36942G>T:p.(=)
Pathogenicity Data:
Best Score: 0.0429877
REMM: 0.043
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94839057-T-A [0/1] rs1433335904
Variant score: 0.041
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-36774T>A:p.(=)
Pathogenicity Data:
Best Score: 0.0407056
REMM: 0.041
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94836729-G-A [0/1] rs1254831195
Variant score: 0.039
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-39102G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0392988
REMM: 0.039
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT INS 4-94836974-T-TA [0/1] rs769694750
Variant score: 0.038
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-38857_-182-38856insA:p.(=)
Pathogenicity Data:
Best Score: 0.0380794
REMM: 0.038
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94840158-T-A [0/1] rs28885478
Variant score: 0.037
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-35673T>A:p.(=)
Pathogenicity Data:
Best Score: 0.0367845
REMM: 0.037
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT DEL 4-94840867-TTC-T [0|1] rs747635248
Variant score: 0.037
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-34963_-182-34962del:p.(=)
Pathogenicity Data:
Best Score: 0.036646
REMM: 0.037
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94839774-T-G [0|1] rs548305893
Variant score: 0.036
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-36057T>G:p.(=)
Pathogenicity Data:
Best Score: 0.0358734
REMM: 0.036
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94839168-C-G [0/1] rs796379699
Variant score: 0.035
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-36663C>G:p.(=)
Pathogenicity Data:
Best Score: 0.034969
REMM: 0.035
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94839775-T-G [0|1] rs568117730
Variant score: 0.033
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-36056T>G:p.(=)
Pathogenicity Data:
Best Score: 0.0334151
REMM: 0.033
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94840611-C-T [0|1] rs1320082631
Variant score: 0.033
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-35220C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0329147
REMM: 0.033
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94837496-G-A [0|1] rs1342906708
Variant score: 0.032
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-38335G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0325044
REMM: 0.033
Frequency Data:
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 0.0015%
gnomAD_G_SAS: 0.0455%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94839202-G-A [0/1] rs796988125
Variant score: 0.032
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-36629G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0319821
REMM: 0.032
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94840551-G-A [0/1] rs912866864
Variant score: 0.032
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-35280G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0319143
REMM: 0.032
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94840667-A-C [0/1] rs186611103
Variant score: 0.032
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-35164A>C:p.(=)
Pathogenicity Data:
Best Score: 0.0315282
REMM: 0.032
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94837485-G-A [0|1] rs1437383490
Variant score: 0.031
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-38346G>A:p.(=)
Pathogenicity Data:
Best Score: 0.031398
REMM: 0.031
Frequency Data:
gnomAD_G_EAS: 0.0774%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94836785-G-A [0|1] rs1432741933
Variant score: 0.029
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-39046G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0294929
REMM: 0.029
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94836786-T-G [0|1] rs1174047462
Variant score: 0.029
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-39045T>G:p.(=)
Pathogenicity Data:
Best Score: 0.0288595
REMM: 0.029
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94840130-A-T [0|1] rs28784882
Variant score: 0.029
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-35701A>T:p.(=)
Pathogenicity Data:
Best Score: 0.0287044
REMM: 0.029
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94837413-G-C [0|1] rs1361696498
Variant score: 0.028
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-38418G>C:p.(=)
Pathogenicity Data:
Best Score: 0.0279484
REMM: 0.028
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94836790-C-T [0|1] rs1431573054
Variant score: 0.026
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-39041C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0263976
REMM: 0.026
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94840621-T-C [0|1] rs1326774497
Variant score: 0.026
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-35210T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0255099
REMM: 0.026
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT INS 4-94837421-C-CGT [0|1] rs1164697263
Variant score: 0.025
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-38410_-182-38409insGT:p.(=)
Pathogenicity Data:
Best Score: 0.0254476
REMM: 0.025
Frequency Data:
gnomAD_G_AMR: 0.0183%
FIVE_PRIME_UTR_INTRON_VARIANT INS 4-94837424-C-CTT [0/1] rs199624774
Variant score: 0.024
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-38407_-182-38406insTT:p.(=)
Pathogenicity Data:
Best Score: 0.0238762
REMM: 0.024
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94837424-C-T [0/1] rs866469163
Variant score: 0.024
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-38407C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0238762
REMM: 0.024
Frequency Data:
gnomAD_G_AMR: 0.0142%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94840623-T-G [0|1] rs1399066653
Variant score: 0.024
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-35208T>G:p.(=)
Pathogenicity Data:
Best Score: 0.0235099
REMM: 0.024
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT INS 4-95043181-C-CA [0/1]
Variant score: 0.021
Transcripts:
BMPR1B:ENST00000515059.6:c.-18+47047_-18+47048insA:p.(=)
Pathogenicity Data:
Best Score: 0.02135
REMM: 0.021
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94838923-T-C [0|1]
Variant score: 0.020
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-36908T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0196544
REMM: 0.020
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94836757-T-G [0/1] rs544679811
Variant score: 0.019
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-39074T>G:p.(=)
Pathogenicity Data:
Best Score: 0.0192544
REMM: 0.019
Frequency Data:
gnomAD_G_AFR: 0.0328%
gnomAD_G_AMR: 0.0068%
gnomAD_G_NFE: 0.0137%
gnomAD_G_SAS: 0.1775%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94836682-C-T [0|1] rs1399971025
Variant score: 0.018
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-39149C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0182988
REMM: 0.018
Frequency Data:
gnomAD_G_AFR: 0.0385%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.0092%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94841072-T-C [0/1] rs553547224
Variant score: 0.018
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-34759T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0191417
REMM: 0.019
Frequency Data:
gnomAD_G_AFR: 0.0698%
gnomAD_G_AMR: 0.1210%
gnomAD_G_EAS: 0.0965%
gnomAD_G_NFE: 0.3881%
gnomAD_G_SAS: 0.2174%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94839682-G-A [0/1] rs868050972
Variant score: 0.017
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-36149G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0174817
REMM: 0.017
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94840380-G-C [0/1] rs189799019
Variant score: 0.017
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-35451G>C:p.(=)
Pathogenicity Data:
Best Score: 0.0174655
REMM: 0.017
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-95141265-T-C [0/1] rs561625167
Variant score: 0.016
Transcripts:
BMPR1B:ENST00000515059.6:c.1077-7483T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0187631
REMM: 0.019
Frequency Data:
UK10K: 0.2116%
gnomAD_G_AFR: 0.0505%
gnomAD_G_AMR: 0.3203%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.2866%
gnomAD_G_SAS: 0.6421%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-95030198-A-G [0/1] rs186640504
Variant score: 0.016
Transcripts:
BMPR1B:ENST00000515059.6:c.-18+34064A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0185988
REMM: 0.019
Frequency Data:
gnomAD_G_AFR: 0.6066%
gnomAD_G_AMR: 0.3405%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.2720%
gnomAD_G_SAS: 0.7273%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94840132-G-C [0|1] rs28879820
Variant score: 0.015
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-35699G>C:p.(=)
Pathogenicity Data:
Best Score: 0.0150107
REMM: 0.015
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94841078-T-G [1/1] rs1210376092
Variant score: 0.015
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-34753T>G:p.(=)
Pathogenicity Data:
Best Score: 0.0238631
REMM: 0.024
Frequency Data:
gnomAD_G_AFR: 0.9507%
gnomAD_G_AMR: 0.9273%
gnomAD_G_EAS: 0.0967%
gnomAD_G_NFE: 1.3360%
gnomAD_G_SAS: 1.3362%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94840516-C-T [0/1] rs1255651414
Variant score: 0.014
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-35315C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0141361
REMM: 0.014
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94837537-T-A [0/1] rs368971758
Variant score: 0.013
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-38294T>A:p.(=)
Pathogenicity Data:
Best Score: 0.013831
REMM: 0.014
Frequency Data:
gnomAD_G_AFR: 0.2238%
gnomAD_G_AMR: 0.0553%
gnomAD_G_EAS: 0.0387%
gnomAD_G_NFE: 0.0140%
FIVE_PRIME_UTR_INTRON_VARIANT DEL 4-94836609-GT-G [0|1] rs558628465
Variant score: 0.013
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-39221del:p.(=)
Pathogenicity Data:
Best Score: 0.0129377
REMM: 0.013
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94837482-G-T [0|1] rs1333050953
Variant score: 0.009
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-38349G>T:p.(=)
Pathogenicity Data:
Best Score: 0.00891151
REMM: 0.009
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94838592-G-C [0|1]
Variant score: 0.009
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-37239G>C:p.(=)
Pathogenicity Data:
Best Score: 0.00874008
REMM: 0.009
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94836686-G-A [0|1] rs370215860
Variant score: 0.007
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-39145G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00673095
REMM: 0.007
Frequency Data:
gnomAD_G_AFR: 0.0025%
gnomAD_G_AMR: 0.0615%
gnomAD_G_NFE: 0.0076%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94838607-C-G [0/1]
Variant score: 0.007
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-37224C>G:p.(=)
Pathogenicity Data:
Best Score: 0.00660794
REMM: 0.007
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94837393-A-C [0|1] rs188320865
Variant score: 0.006
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-38438A>C:p.(=)
Pathogenicity Data:
Best Score: 0.0061754
REMM: 0.006
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-95127457-G-T [0/1] rs184323867
Variant score: 0.006
Transcripts:
BMPR1B:ENST00000515059.6:c.585+2336G>T:p.(=)
Pathogenicity Data:
Best Score: 0.00665278
REMM: 0.007
Frequency Data:
gnomAD_G_AFR: 0.0410%
gnomAD_G_AMR: 0.3079%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.2663%
gnomAD_G_SAS: 0.6437%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94840900-C-A [0/1] rs1221861413
Variant score: 0.005
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-34931C>A:p.(=)
Pathogenicity Data:
Best Score: 0.00553333
REMM: 0.006
Frequency Data:
gnomAD_G_AFR: 0.0632%
gnomAD_G_AMR: 0.0350%
gnomAD_G_NFE: 0.0430%
gnomAD_G_SAS: 0.0462%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-95055331-G-A [0/1] rs560645968
Variant score: 0.005
Transcripts:
BMPR1B:ENST00000515059.6:c.-17-49077G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00537063
REMM: 0.005
Frequency Data:
UK10K: 0.0793%
gnomAD_G_AFR: 0.0337%
gnomAD_G_AMR: 0.0851%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.1118%
gnomAD_G_SAS: 0.6858%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94838628-T-C [0/1] rs1363521791
Variant score: 0.004
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-37203T>C:p.(=)
Pathogenicity Data:
Best Score: 0.003975
REMM: 0.004
Frequency Data:
gnomAD_G_NFE: 0.0031%
gnomAD_G_SAS: 0.0232%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94840761-C-G [1|0] rs1338163277
Variant score: 0.003
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-35070C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0136825
REMM: 0.014
Frequency Data:
gnomAD_G_AFR: 1.7138%
gnomAD_G_AMR: 1.4585%
gnomAD_G_NFE: 1.9271%
gnomAD_G_SAS: 1.6454%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94841012-G-A [0/1] rs372391482
Variant score: 0.003
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-34819G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00321508
REMM: 0.003
Frequency Data:
gnomAD_G_AFR: 0.5550%
gnomAD_G_AMR: 0.5014%
gnomAD_G_EAS: 0.6194%
gnomAD_G_NFE: 0.6979%
gnomAD_G_SAS: 0.4971%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94840795-G-A [0|1] rs1420945520
Variant score: 0.002
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-35036G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0156841
REMM: 0.016
Frequency Data:
gnomAD_G_AFR: 1.7247%
gnomAD_G_AMR: 1.5481%
gnomAD_G_EAS: 0.0580%
gnomAD_G_NFE: 1.9911%
gnomAD_G_SAS: 1.9863%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94838675-G-A [0|1] rs1318322664
Variant score: 0.002
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-37156G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00191071
REMM: 0.002
Frequency Data:
gnomAD_G_AFR: 0.0027%
gnomAD_G_NFE: 0.0062%
gnomAD_G_SAS: 0.0234%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94837886-T-G [0/1] rs549728785
Variant score: 0.002
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-37945T>G:p.(=)
Pathogenicity Data:
Best Score: 0.00173095
REMM: 0.002
Frequency Data:
gnomAD_G_AFR: 0.0159%
gnomAD_G_AMR: 0.0208%
gnomAD_G_NFE: 0.0263%
gnomAD_G_SAS: 0.0937%
FIVE_PRIME_UTR_INTRON_VARIANT DEL 4-95086998-CT-C [0/1]
Variant score: 0.002
Transcripts:
BMPR1B:ENST00000515059.6:c.-17-17409del:p.(=)
Pathogenicity Data:
Best Score: 0.00158333
REMM: 0.002
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT DEL 4-95086998-CTT-C [0/1]
Variant score: 0.002
Transcripts:
BMPR1B:ENST00000515059.6:c.-17-17409_-17-17408del:p.(=)
Pathogenicity Data:
Best Score: 0.00158333
REMM: 0.002
Frequency Data:
No frequency data
DOWNSTREAM_GENE_VARIANT DEL 4-95160540-TTCCTTCCTTCCC-T [0/1] rs1298479897
Variant score: 0.002
Transcripts:
BMPR1B:ENST00000515059.6::
Pathogenicity Data:
Best Score: 0.00154444
REMM: 0.002
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94840696-T-C [0/1] rs1191855159
Variant score: 0.001
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-35135T>C:p.(=)
Pathogenicity Data:
Best Score: 0.00118333
REMM: 0.001
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94839390-G-A [0/1] rs1315992643
Variant score: 0.001
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-36441G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00183333
REMM: 0.002
Frequency Data:
gnomAD_G_AFR: 1.4046%
gnomAD_G_AMR: 0.5413%
gnomAD_G_EAS: 0.0387%
gnomAD_G_NFE: 0.3920%
gnomAD_G_SAS: 0.5332%
DOWNSTREAM_GENE_VARIANT DEL 4-95160537-CCCTTCCTT-C [0/1]
Variant score: 0.001
Transcripts:
BMPR1B:ENST00000515059.6::
Pathogenicity Data:
Best Score: 0.00104444
REMM: 0.001
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94838115-A-G [0/1] rs1484223835
Variant score: 0.001
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-37716A>G:p.(=)
Pathogenicity Data:
Best Score: 0.001
REMM: 0.001
Frequency Data:
gnomAD_G_AFR: 0.0660%
gnomAD_G_AMR: 0.0069%
gnomAD_G_EAS: 0.0582%
gnomAD_G_NFE: 0.0046%
gnomAD_G_SAS: 0.0927%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94838971-A-G [0/1] rs1560508768
Variant score: 0.001
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-36860A>G:p.(=)
Pathogenicity Data:
Best Score: 7.0E-4
REMM: 0.001
Frequency Data:
gnomAD_G_NFE: 0.0017%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94837792-C-T [0/1] rs374344881
Variant score: 0.001
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-38039C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00143333
REMM: 0.001
Frequency Data:
gnomAD_G_AFR: 1.6332%
gnomAD_G_AMR: 0.2381%
gnomAD_G_EAS: 0.0195%
gnomAD_G_NFE: 0.0079%
gnomAD_G_SAS: 0.0237%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94788458-A-C [0/1]
Variant score: 0.001
Transcripts:
BMPR1B:ENST00000515059.6:c.-183+30390A>C:p.(=)
Pathogenicity Data:
Best Score: 6.0E-4
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 4-95116421-G-GCGCACA [0/1]
Variant score: 0.001
Transcripts:
BMPR1B:ENST00000515059.6:c.349+634_349+635insCGCACA:p.(=)
Pathogenicity Data:
Best Score: 0.001625
REMM: 0.002
Frequency Data:
gnomAD_G_AFR: 1.6303%
gnomAD_G_AMR: 1.7343%
gnomAD_G_EAS: 0.1628%
gnomAD_G_NFE: 1.0449%
gnomAD_G_SAS: 1.3200%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94838912-T-C [0|1]
Variant score: 0.000
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-36919T>C:p.(=)
Pathogenicity Data:
Best Score: 4.5E-4
REMM: 0.000
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94838268-A-C [1/1] rs79491727
Variant score: 0.000
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-37563A>C:p.(=)
Pathogenicity Data:
Best Score: 2.5E-4
REMM: 0.000
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94838061-G-T [0/1] rs1288559313
Variant score: 0.000
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-37770G>T:p.(=)
Pathogenicity Data:
Best Score: 2.5E-4
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0104%
gnomAD_G_AMR: 0.0068%
gnomAD_G_EAS: 0.0387%
gnomAD_G_NFE: 0.0077%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 4-95148979-C-G [0/1] rs191183602
Variant score: 0.000
Transcripts:
BMPR1B:ENST00000515059.6:c.1252+56C>G:p.(=)
Pathogenicity Data:
Best Score: 2.22222E-4
REMM: 0.000
Frequency Data:
UK10K: 0.1984%
gnomAD_E_AFR: 0.0242%
gnomAD_E_AMR: 0.1769%
gnomAD_E_NFE: 0.2351%
gnomAD_E_SAS: 0.8211%
gnomAD_G_AFR: 0.0409%
gnomAD_G_AMR: 0.3073%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.2646%
gnomAD_G_SAS: 0.6421%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94838818-G-C [0/1] rs1223293051
Variant score: 0.000
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-37013G>C:p.(=)
Pathogenicity Data:
Best Score: 2.0E-4
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 1.3099%
gnomAD_G_AMR: 0.4489%
gnomAD_G_EAS: 0.0202%
gnomAD_G_NFE: 0.2689%
gnomAD_G_SAS: 0.0250%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94836602-A-G [0|1] rs377353488
Variant score: 0.000
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-39229A>G:p.(=)
Pathogenicity Data:
Best Score: 1.0E-4
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.2571%
gnomAD_G_AMR: 0.1542%
gnomAD_G_EAS: 0.0785%
gnomAD_G_NFE: 0.2177%
gnomAD_G_SAS: 0.3984%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94838590-T-G [0|1] rs369884826
Variant score: 0.000
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-37241T>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_NFE: 0.0016%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-94838669-A-G [0|1] rs1413592358
Variant score: 0.000
Transcripts:
BMPR1B:ENST00000515059.6:c.-182-37162A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.6035%
gnomAD_G_AMR: 0.0846%
gnomAD_G_EAS: 0.1592%
gnomAD_G_SAS: 0.0236%
FIVE_PRIME_UTR_INTRON_VARIANT INS 4-94908061-T-TAAAAAAAAAAA [0/1] rs571793477
Variant score: 0.000
Transcripts:
BMPR1B:ENST00000515059.6:c.-113+32161_-113+32162insAAAAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.8778%
gnomAD_G_AMR: 0.2315%
gnomAD_G_NFE: 0.4064%
gnomAD_G_SAS: 0.0929%
FIVE_PRIME_UTR_INTRON_VARIANT INS 4-94981004-C-CGCGCGCGT [1|1]
Variant score: 0.000
Transcripts:
BMPR1B:ENST00000515059.6:c.-112-15036_-112-15035insGCGCGCGT:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-95040047-C-T [0/1] rs555635453
Variant score: 0.000
Transcripts:
BMPR1B:ENST00000515059.6:c.-18+43913C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.0397%
gnomAD_G_AFR: 0.0072%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.0235%
gnomAD_G_SAS: 0.2486%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 4-95079306-A-G [0/1] rs941084308
Variant score: 0.000
Transcripts:
BMPR1B:ENST00000515059.6:c.-17-25102A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0048%

GRAP

Exomiser Score: 0.183 (p=2.1E-1)

Phenotype Score: 0.251

Variant Score: 1.000

Phenotype matches:
Proximity score 0.502 in interactome to LHX4 and phenotypic similarity 0.676 to Combined pituitary hormone deficiencies, genetic forms associated with LHX4.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
HP:0006625, Multifocal breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
Known diseases - observed variants incompatible with mode of inheritance:
OMIM:618456 Deafness, autosomal recessive 114 - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.183 (p=2.1E-1)

Phenotype Score: 0.251

Variant Score: 1.000

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 17-19024372-T-A [0/1] rs370564476
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PP5]
ClinVar: LIKELY_PATHOGENIC (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 1.000 CONTRIBUTING VARIANT WHITELIST VARIANT
Transcripts:
GRAP:ENST00000284154.10:c.311A>T:p.(Gln104Leu)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_NFE: 0.0012%
gnomAD_G_NFE: 0.0059%

GOLGA3

Exomiser Score: 0.178 (p=2.1E-1)

Phenotype Score: 0.515

Variant Score: 0.697

Phenotype matches:
Proximity score 0.515 in interactome to COG7 and phenotypic similarity 0.643 to Congenital disorder of glycosylation, type IIe associated with COG7.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.178 (p=2.1E-1)

Phenotype Score: 0.515

Variant Score: 0.697

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-132813721-CT-C [1/1] rs10717082
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.697 CONTRIBUTING VARIANT
Transcripts:
GOLGA3:ENST00000450791.8:c.407-303del:p.(=)
Pathogenicity Data:
Best Score: 0.697336
REMM: 0.697
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.125 (p=2.4E-1)

Phenotype Score: 0.515

Variant Score: 0.652

No phenotype matches to diseases with this MOI.
Variants contributing to score:
DOWNSTREAM_GENE_VARIANT SNV 12-132766398-C-T [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.652 CONTRIBUTING VARIANT
Transcripts:
GOLGA3:ENST00000450791.8::
Pathogenicity Data:
Best Score: 0.652132
REMM: 0.652
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-132815524-A-G [0/1] rs551861613
Variant score: 0.356
Transcripts:
GOLGA3:ENST00000450791.8:c.406+1016T>C:p.(=)
Pathogenicity Data:
Best Score: 0.37447
REMM: 0.374
Frequency Data:
UK10K: 0.1455%
gnomAD_G_AFR: 0.0505%
gnomAD_G_AMR: 0.0196%
gnomAD_G_NFE: 0.2645%
gnomAD_G_SAS: 0.3106%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-132817281-G-A [0|1]
Variant score: 0.343
Transcripts:
GOLGA3:ENST00000450791.8:c.134-469C>T:p.(=)
Pathogenicity Data:
Best Score: 0.343352
REMM: 0.343
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-132817305-G-C [1|1]
Variant score: 0.329
Transcripts:
GOLGA3:ENST00000450791.8:c.134-493C>G:p.(=)
Pathogenicity Data:
Best Score: 0.328594
REMM: 0.329
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-132817279-C-T [0|1] rs71439321
Variant score: 0.326
Transcripts:
GOLGA3:ENST00000450791.8:c.134-467G>A:p.(=)
Pathogenicity Data:
Best Score: 0.325806
REMM: 0.326
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-132817475-A-ACCCGCCCT [0/1] rs1276818223
Variant score: 0.305
Transcripts:
GOLGA3:ENST00000450791.8:c.134-664_134-663insAGGGCGGG:p.(=)
Pathogenicity Data:
Best Score: 0.305237
REMM: 0.305
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-132817347-G-C [0/1]
Variant score: 0.277
Transcripts:
GOLGA3:ENST00000450791.8:c.134-535C>G:p.(=)
Pathogenicity Data:
Best Score: 0.277413
REMM: 0.277
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-132805478-G-A [1/1] rs7132014
Variant score: 0.274
Transcripts:
GOLGA3:ENST00000450791.8:c.1291-456C>T:p.(=)
Pathogenicity Data:
Best Score: 0.273938
REMM: 0.274
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-132817776-G-A [1/1]
Variant score: 0.272
Transcripts:
GOLGA3:ENST00000450791.8:c.134-964C>T:p.(=)
Pathogenicity Data:
Best Score: 0.271832
REMM: 0.272
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-132817785-T-A [1/1]
Variant score: 0.247
Transcripts:
GOLGA3:ENST00000450791.8:c.134-973A>T:p.(=)
Pathogenicity Data:
Best Score: 0.246836
REMM: 0.247
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-132817380-G-A [1/1] rs11616015
Variant score: 0.236
Transcripts:
GOLGA3:ENST00000450791.8:c.134-568C>T:p.(=)
Pathogenicity Data:
Best Score: 0.286174
REMM: 0.286
Frequency Data:
gnomAD_G_NFE: 0.8333%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-132817851-T-A [1/1] rs28420228
Variant score: 0.235
Transcripts:
GOLGA3:ENST00000450791.8:c.134-1039A>T:p.(=)
Pathogenicity Data:
Best Score: 0.234615
REMM: 0.235
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-132817290-T-A [1|1]
Variant score: 0.224
Transcripts:
GOLGA3:ENST00000450791.8:c.134-478A>T:p.(=)
Pathogenicity Data:
Best Score: 0.224396
REMM: 0.224
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-132817806-C-G [1/1] rs1316317823
Variant score: 0.224
Transcripts:
GOLGA3:ENST00000450791.8:c.134-994G>C:p.(=)
Pathogenicity Data:
Best Score: 0.223603
REMM: 0.224
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-132817859-G-A [1/1] rs182481230
Variant score: 0.220
Transcripts:
GOLGA3:ENST00000450791.8:c.134-1047C>T:p.(=)
Pathogenicity Data:
Best Score: 0.219533
REMM: 0.220
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-132793367-G-C [1/1]
Variant score: 0.218
Transcripts:
GOLGA3:ENST00000450791.8:c.2470-2074C>G:p.(=)
Pathogenicity Data:
Best Score: 0.217725
REMM: 0.218
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-132817265-A-G [1|1]
Variant score: 0.197
Transcripts:
GOLGA3:ENST00000450791.8:c.134-453T>C:p.(=)
Pathogenicity Data:
Best Score: 0.196867
REMM: 0.197
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-132817272-C-G [0|1]
Variant score: 0.193
Transcripts:
GOLGA3:ENST00000450791.8:c.134-460G>C:p.(=)
Pathogenicity Data:
Best Score: 0.193321
REMM: 0.193
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-132791050-C-CAA [0/1]
Variant score: 0.191
Transcripts:
GOLGA3:ENST00000450791.8:c.2547+165_2547+166insTT:p.(=)
Pathogenicity Data:
Best Score: 0.190624
REMM: 0.191
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-132791050-C-CAAA [0/1]
Variant score: 0.191
Transcripts:
GOLGA3:ENST00000450791.8:c.2547+165_2547+166insTTT:p.(=)
Pathogenicity Data:
Best Score: 0.190624
REMM: 0.191
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-132817809-G-C [1/1]
Variant score: 0.163
Transcripts:
GOLGA3:ENST00000450791.8:c.134-997C>G:p.(=)
Pathogenicity Data:
Best Score: 0.163157
REMM: 0.163
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-132817833-C-G [1/1]
Variant score: 0.160
Transcripts:
GOLGA3:ENST00000450791.8:c.134-1021G>C:p.(=)
Pathogenicity Data:
Best Score: 0.160307
REMM: 0.160
Frequency Data:
No frequency data
THREE_PRIME_UTR_EXON_VARIANT SNV 12-132771892-G-A [0/1] rs577032884
Variant score: 0.154
Transcripts:
GOLGA3:ENST00000450791.8:c.*1213C>T:p.(=)
Pathogenicity Data:
Best Score: 0.178746
REMM: 0.179
Frequency Data:
UK10K: 0.1455%
gnomAD_E_NFE: 0.6944%
gnomAD_G_AFR: 0.0529%
gnomAD_G_AMR: 0.0196%
gnomAD_G_NFE: 0.2529%
gnomAD_G_SAS: 0.3108%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-132817609-T-C [0/1] rs374474842
Variant score: 0.154
Transcripts:
GOLGA3:ENST00000450791.8:c.134-797A>G:p.(=)
Pathogenicity Data:
Best Score: 0.153583
REMM: 0.154
Frequency Data:
No frequency data
DOWNSTREAM_GENE_VARIANT SNV 12-132765078-C-T [0/1] rs549297224
Variant score: 0.002
Transcripts:
GOLGA3:ENST00000450791.8::
Pathogenicity Data:
Best Score: 0.002
REMM: 0.002
Frequency Data:
gnomAD_G_AFR: 0.0602%
gnomAD_G_AMR: 0.0981%
gnomAD_G_EAS: 0.1353%
gnomAD_G_NFE: 0.2779%
gnomAD_G_SAS: 0.3106%

STX11

Exomiser Score: 0.171 (p=2.1E-1)

Phenotype Score: 0.502

Variant Score: 0.707

Phenotype matches:
Proximity score 0.502 in interactome to VAMP7 and phenotypic similarity 0.614 to 46,XY partial gonadal dysgenesis associated with VAMP7.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Known diseases:
OMIM:603552 Hemophagocytic lymphohistiocytosis, familial, 4 - autosomal recessive
ORPHA:540 Familial hemophagocytic lymphohistiocytosis - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.171 (p=2.1E-1)

Phenotype Score: 0.502

Variant Score: 0.707

No phenotype matches to diseases with this MOI.
Variants contributing to score:
INTERGENIC_VARIANT SNV 6-144141194-A-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.749 CONTRIBUTING VARIANT
Transcripts:
STX11:ENST00000367568.5::
Pathogenicity Data:
Best Score: 0.749444
REMM: 0.749
Frequency Data:
No frequency data
DOWNSTREAM_GENE_VARIANT SNV 6-144195037-G-A [0/1] rs867703612
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.664 CONTRIBUTING VARIANT
Transcripts:
STX11:ENST00000367568.5::
Pathogenicity Data:
Best Score: 0.6676
REMM: 0.668
Frequency Data:
gnomAD_G_AFR: 0.0072%
gnomAD_G_AMR: 0.0328%
gnomAD_G_NFE: 0.0368%
gnomAD_G_SAS: 0.0416%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.022 (p=3.9E-1)

Phenotype Score: 0.251

Variant Score: 0.749

No phenotype matches to diseases with this MOI.
Variants contributing to score:
INTERGENIC_VARIANT SNV 6-144141194-A-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.749 CONTRIBUTING VARIANT
Transcripts:
STX11:ENST00000367568.5::
Pathogenicity Data:
Best Score: 0.749444
REMM: 0.749
Frequency Data:
No frequency data
Other passed variants:
INTERGENIC_VARIANT INS 6-144132064-A-AAATAAT [0/1] rs71546214
Variant score: 0.557
Transcripts:
STX11:ENST00000367568.5::
Pathogenicity Data:
Best Score: 0.556667
REMM: 0.557
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 6-144206118-T-C [0/1]
Variant score: 0.531
Transcripts:
STX11:ENST00000367568.5::
Pathogenicity Data:
Best Score: 0.531399
REMM: 0.531
Frequency Data:
No frequency data
DOWNSTREAM_GENE_VARIANT SNV 6-144193041-G-A [0/1] rs542690944
Variant score: 0.471
Transcripts:
STX11:ENST00000367568.5::
Pathogenicity Data:
Best Score: 0.481203
REMM: 0.481
Frequency Data:
gnomAD_G_AFR: 0.0096%
gnomAD_G_NFE: 0.0559%
gnomAD_G_SAS: 0.1452%
FIVE_PRIME_UTR_INTRON_VARIANT DEL 6-144155940-ATCTT-A [0/1] rs72252665
Variant score: 0.435
Transcripts:
STX11:ENST00000367568.5:c.-6+5238_-6+5241del:p.(=)
Pathogenicity Data:
Best Score: 0.550982
REMM: 0.551
Frequency Data:
UK10K: 0.9389%
INTERGENIC_VARIANT DEL 6-144205215-CT-C [0/1] rs532570129
Variant score: 0.387
Transcripts:
STX11:ENST00000367568.5::
Pathogenicity Data:
Best Score: 0.389113
REMM: 0.389
Frequency Data:
gnomAD_G_AFR: 0.0120%
gnomAD_G_AMR: 0.0327%
gnomAD_G_NFE: 0.0368%
gnomAD_G_SAS: 0.0416%

BRAF

Exomiser Score: 0.168 (p=2.2E-1)

Phenotype Score: 0.577

Variant Score: 0.619

Phenotype matches:
Phenotypic similarity 0.577 to LEOPARD syndrome 3 associated with BRAF.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0006610, Wide intermamillary distance
HP:0006625, Multifocal breast carcinoma - HP:0006610, Wide intermamillary distance
Phenotypic similarity 0.329 to mouse mutant involving BRAF.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000074, abnormal neurocranium morphology
HP:0006625, Multifocal breast carcinoma - MP:0000074, abnormal neurocranium morphology
Known diseases:
OMIM:114500 Colorectal cancer, somatic - autosomal dominant
OMIM:115150 Cardiofaciocutaneous syndrome - autosomal dominant
OMIM:155600 Melanoma, malignant, somatic - autosomal dominant
OMIM:211980 Adenocarcinoma of lung, somatic - autosomal dominant
OMIM:613706 Noonan syndrome 7 - autosomal dominant
OMIM:613707 LEOPARD syndrome 3 - autosomal dominant
ORPHA:1340 Cardiofaciocutaneous syndrome - autosomal dominant
ORPHA:500 Noonan syndrome with multiple lentigines - autosomal dominant
ORPHA:626 Large congenital melanocytic nevus (unconfirmed)
ORPHA:626 Large congenital melanocytic nevus (unconfirmed)
ORPHA:96253 Cushing disease (unconfirmed)
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.168 (p=2.2E-1)

Phenotype Score: 0.577

Variant Score: 0.619

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.577 to OMIM:613707 LEOPARD syndrome 3
Phenotypic similarity 0.525 to OMIM:613706 Noonan syndrome 7
Phenotypic similarity 0.525 to OMIM:115150 Cardiofaciocutaneous syndrome
Phenotypic similarity 0.448 to ORPHA:500 Noonan syndrome with multiple lentigines
Phenotypic similarity 0.444 to ORPHA:1340 Cardiofaciocutaneous syndrome
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-140800645-T-C [0/1] rs1443068879
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.619 CONTRIBUTING VARIANT
Transcripts:
BRAF:ENST00000644969.2:c.861-164A>G:p.(=)
BRAF:ENST00000646891.2:c.861-164A>G:p.(=)
Pathogenicity Data:
Best Score: 0.62081
REMM: 0.621
Frequency Data:
gnomAD_G_NFE: 0.0015%
gnomAD_G_SAS: 0.0207%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.003 (p=6.2E-1)

Phenotype Score: 0.165

Variant Score: 0.612

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-140798272-C-CTTTTTTTTTTTT [1/1] rs10525418
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.612 CONTRIBUTING VARIANT
Transcripts:
BRAF:ENST00000644969.2:c.980+2089_980+2090insAAAAAAAAAAAA:p.(=)
BRAF:ENST00000646891.2:c.980+2089_980+2090insAAAAAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.61227
REMM: 0.612
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-140913469-C-CTTTT [0/1] rs369746551
Variant score: 0.581
Transcripts:
BRAF:ENST00000644969.2:c.138+11096_138+11097insAAAA:p.(=)
BRAF:ENST00000646891.2:c.138+11096_138+11097insAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.827156
REMM: 0.827
Frequency Data:
gnomAD_G_AFR: 1.0533%
gnomAD_G_AMR: 1.1635%
gnomAD_G_EAS: 1.0884%
gnomAD_G_NFE: 0.7425%
gnomAD_G_SAS: 0.4195%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-140732217-T-C [0/1]
Variant score: 0.530
Transcripts:
BRAF:ENST00000644969.2:c.2401+2400A>G:p.(=)
BRAF:ENST00000646891.2:c.*2380A>G:p.(=)
Pathogenicity Data:
Best Score: 0.530081
REMM: 0.530
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-140821294-AT-A [1/1] rs58690200
Variant score: 0.094
Transcripts:
BRAF:ENST00000644969.2:c.505-12300del:p.(=)
BRAF:ENST00000646891.2:c.505-12300del:p.(=)
Pathogenicity Data:
Best Score: 0.094104
REMM: 0.094
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-140801053-T-C [0/1] rs1008305025
Variant score: 0.024
Transcripts:
BRAF:ENST00000644969.2:c.860+359A>G:p.(=)
BRAF:ENST00000646891.2:c.860+359A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0246917
REMM: 0.025
Frequency Data:
gnomAD_E_EAS: 0.1015%
gnomAD_G_EAS: 0.0192%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-140867566-G-T [0/1] rs768432549
Variant score: 0.003
Transcripts:
BRAF:ENST00000644969.2:c.139-17354C>A:p.(=)
BRAF:ENST00000646891.2:c.139-17354C>A:p.(=)
Pathogenicity Data:
Best Score: 0.00254286
REMM: 0.003
Frequency Data:
UK10K: 0.0132%
gnomAD_G_NFE: 0.0029%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-140911988-G-A [0/1] rs972358085
Variant score: 0.002
Transcripts:
BRAF:ENST00000644969.2:c.138+12578C>T:p.(=)
BRAF:ENST00000646891.2:c.138+12578C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0018
REMM: 0.002
Frequency Data:
gnomAD_G_NFE: 0.0015%

PAN2

Exomiser Score: 0.167 (p=2.2E-1)

Phenotype Score: 0.501

Variant Score: 0.704

Phenotype matches:
Phenotypic similarity 0.199 to mouse mutant involving PAN2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0005011, increased eosinophil cell number
HP:0006625, Multifocal breast carcinoma - MP:0005011, increased eosinophil cell number
Proximity score 0.501 in interactome to EIF4A2 and phenotypic similarity 0.643 to Neurodevelopmental disorder with hypotonia and speech delay, with or without seizures associated with EIF4A2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.167 (p=2.2E-1)

Phenotype Score: 0.501

Variant Score: 0.704

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-56323661-A-AC [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.704 CONTRIBUTING VARIANT
Transcripts:
PAN2:ENST00000440411.8:c.2173-64_2173-63insG:p.(=)
Pathogenicity Data:
Best Score: 0.704488
REMM: 0.704
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.109 (p=2.6E-1)

Phenotype Score: 0.501

Variant Score: 0.651

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-56323661-A-AC [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.704 CONTRIBUTING VARIANT
Transcripts:
PAN2:ENST00000440411.8:c.2173-64_2173-63insG:p.(=)
Pathogenicity Data:
Best Score: 0.704488
REMM: 0.704
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 12-56327481-T-G [0/1] rs561402020
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.598 CONTRIBUTING VARIANT
Transcripts:
PAN2:ENST00000440411.8:c.802A>C:p.(Lys268Gln)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.0264%
gnomAD_E_AFR: 0.0060%
gnomAD_E_AMR: 0.0022%
gnomAD_E_NFE: 0.0052%
gnomAD_E_SAS: 0.0046%
gnomAD_G_NFE: 0.0059%
gnomAD_G_SAS: 0.0207%

ITGA2

Exomiser Score: 0.163 (p=2.2E-1)

Phenotype Score: 0.502

Variant Score: 0.701

Phenotype matches:
Proximity score 0.502 in interactome to ITGA3 and phenotypic similarity 0.603 to Epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome associated with ITGA3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.163 (p=2.2E-1)

Phenotype Score: 0.502

Variant Score: 0.701

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-52993160-T-G [0/1] rs557053011
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.713 CONTRIBUTING VARIANT
Transcripts:
ITGA2:ENST00000296585.10:c.64+3628T>G:p.(=)
Pathogenicity Data:
Best Score: 0.781211
REMM: 0.781
Frequency Data:
UK10K: 0.1587%
gnomAD_G_AFR: 0.0217%
gnomAD_G_AMR: 0.0914%
gnomAD_G_NFE: 0.2808%
gnomAD_G_SAS: 0.4973%
CODING_TRANSCRIPT_INTRON_VARIANT INS 5-53004894-G-GTTTTTTTT [0/1] rs548541753
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.688 CONTRIBUTING VARIANT
Transcripts:
ITGA2:ENST00000296585.10:c.64+15362_64+15363insTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.707016
REMM: 0.707
Frequency Data:
gnomAD_G_AFR: 0.0463%
gnomAD_G_EAS: 0.0720%
gnomAD_G_NFE: 0.0288%
gnomAD_G_SAS: 0.1786%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.035 (p=3.5E-1)

Phenotype Score: 0.502

Variant Score: 0.518

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 5-53044274-CAAA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.518 CONTRIBUTING VARIANT
Transcripts:
ITGA2:ENST00000296585.10:c.296-726_296-724del:p.(=)
Pathogenicity Data:
Best Score: 0.518467
REMM: 0.518
Frequency Data:
No frequency data
Other passed variants:
SYNONYMOUS_VARIANT SNV 5-53042118-G-C [0/1] rs745339648
Variant score: 0.100
Transcripts:
ITGA2:ENST00000296585.10:c.192G>C:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_EAS: 0.0101%
gnomAD_E_NFE: 0.0004%
gnomAD_E_SAS: 0.0023%
gnomAD_G_NFE: 0.0015%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-53082734-C-T [0/1] rs932716872
Variant score: 0.003
Transcripts:
ITGA2:ENST00000296585.10:c.3145-606C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00257857
REMM: 0.003
Frequency Data:
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0065%
gnomAD_G_NFE: 0.0015%

NUP210

Exomiser Score: 0.161 (p=2.2E-1)

Phenotype Score: 0.501

Variant Score: 0.699

Phenotype matches:
Proximity score 0.501 in interactome to NUP107 and phenotypic similarity 0.676 to 46,XX gonadal dysgenesis associated with NUP107.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
HP:0006625, Multifocal breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
Proximity score 0.501 in interactome to NUP107 and phenotypic similarity 0.225 to fish mutant of NUP107.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0016453, pharyngeal arch has fewer parts of type chondroblast nuclear pore chondroblast, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0016453, pharyngeal arch has fewer parts of type chondroblast nuclear pore chondroblast, abnormal
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.161 (p=2.2E-1)

Phenotype Score: 0.501

Variant Score: 0.699

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-13419092-G-A [0/1] rs148549332
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.712 CONTRIBUTING VARIANT
Transcripts:
NUP210:ENST00000254508.7:c.167+968C>T:p.(=)
Pathogenicity Data:
Best Score: 0.74311
REMM: 0.743
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.2684%
gnomAD_G_NFE: 0.0853%
gnomAD_G_SAS: 0.0415%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-13325374-C-T [0/1] rs183235143
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.687 CONTRIBUTING VARIANT
Transcripts:
NUP210:ENST00000254508.7:c.4644+421G>A:p.(=)
Pathogenicity Data:
Best Score: 0.761048
REMM: 0.761
Frequency Data:
gnomAD_G_AFR: 0.0144%
gnomAD_G_AMR: 0.5426%
gnomAD_G_NFE: 0.1455%
gnomAD_G_SAS: 0.0829%
Other passed variants:
MISSENSE_VARIANT SNV 3-13341822-C-T [0/1] rs151008831
Variant score: 0.550
Transcripts:
NUP210:ENST00000254508.7:c.3154G>A:p.(Gly1052Ser)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.4761%
gnomAD_E_AFR: 0.0806%
gnomAD_E_AMR: 0.1230%
gnomAD_E_EAS: 0.0050%
gnomAD_E_NFE: 0.4733%
gnomAD_E_SAS: 0.4487%
gnomAD_G_AFR: 0.1059%
gnomAD_G_AMR: 0.0720%
gnomAD_G_NFE: 0.4734%
gnomAD_G_SAS: 0.3523%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 3-13370184-GCCCTACACACCT-G [0/1] rs569907120
Variant score: 0.206
Transcripts:
NUP210:ENST00000254508.7:c.1786+1638_1786+1649del:p.(=)
Pathogenicity Data:
Best Score: 0.797575
REMM: 0.798
Frequency Data:
UK10K: 0.1719%
gnomAD_G_AFR: 0.0265%
gnomAD_G_AMR: 0.6811%
gnomAD_G_EAS: 1.4905%
gnomAD_G_NFE: 0.2118%
gnomAD_G_SAS: 1.8695%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-13355274-T-G [0/1] rs74854851
Variant score: 0.200
Transcripts:
NUP210:ENST00000254508.7:c.2329-1167A>C:p.(=)
Pathogenicity Data:
Best Score: 0.713239
REMM: 0.713
Frequency Data:
UK10K: 0.1984%
gnomAD_G_AFR: 0.0241%
gnomAD_G_AMR: 0.6859%
gnomAD_G_EAS: 1.4853%
gnomAD_G_NFE: 0.2117%
gnomAD_G_SAS: 1.8434%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-13333083-T-A [0/1] rs748635896
Variant score: 0.001
Transcripts:
NUP210:ENST00000254508.7:c.3844-699A>T:p.(=)
Pathogenicity Data:
Best Score: 7.14286E-4
REMM: 0.001
Frequency Data:
UK10K: 0.4761%
gnomAD_G_AFR: 0.1011%
gnomAD_G_AMR: 0.0589%
gnomAD_G_NFE: 0.4528%
gnomAD_G_SAS: 0.3731%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-13407276-G-A [0/1] rs74281335
Variant score: 0.000
Transcripts:
NUP210:ENST00000254508.7:c.168-7415C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.2116%
gnomAD_G_AFR: 0.0265%
gnomAD_G_AMR: 0.7777%
gnomAD_G_EAS: 1.5058%
gnomAD_G_NFE: 0.2234%
gnomAD_G_SAS: 1.9518%

MAP2K3

Exomiser Score: 0.160 (p=2.2E-1)

Phenotype Score: 0.503

Variant Score: 0.697

Phenotype matches:
Proximity score 0.503 in interactome to FASLG and phenotypic similarity 0.876 to Autoimmune lymphoproliferative syndrome associated with FASLG.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010619, Fibroadenoma of the breast
HP:0006625, Multifocal breast carcinoma - HP:0010619, Fibroadenoma of the breast
Proximity score 0.503 in interactome to FASLG and phenotypic similarity 0.220 to mouse mutant of FASLG.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0001541, abnormal osteoclast physiology
HP:0006625, Multifocal breast carcinoma - MP:0001541, abnormal osteoclast physiology
Proximity score 0.503 in interactome to FASLG and phenotypic similarity 0.300 to fish mutant of FASLG.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0000627, notochord bent, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0000627, notochord bent, abnormal
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.160 (p=2.2E-1)

Phenotype Score: 0.503

Variant Score: 0.697

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-21308787-C-CT [0/1] rs5819739
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.697 CONTRIBUTING VARIANT
Transcripts:
MAP2K3:ENST00000342679.9:c.775-3355_775-3354insT:p.(=)
Pathogenicity Data:
Best Score: 0.696971
REMM: 0.697
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.146 (p=2.3E-1)

Phenotype Score: 0.503

Variant Score: 0.685

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-21308787-C-CT [0/1] rs5819739
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.697 CONTRIBUTING VARIANT
Transcripts:
MAP2K3:ENST00000342679.9:c.775-3355_775-3354insT:p.(=)
Pathogenicity Data:
Best Score: 0.696971
REMM: 0.697
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21306324-T-A [0|1] rs77169361
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.674 CONTRIBUTING VARIANT
Transcripts:
MAP2K3:ENST00000342679.9:c.774+1196T>A:p.(=)
Pathogenicity Data:
Best Score: 0.706318
REMM: 0.706
Frequency Data:
gnomAD_G_AFR: 0.0937%
gnomAD_G_AMR: 0.0968%
gnomAD_G_EAS: 0.2935%
gnomAD_G_NFE: 0.0517%
gnomAD_G_SAS: 0.1882%
Other passed variants:
INTERGENIC_VARIANT DEL 17-21333964-CAG-C [0|1]
Variant score: 0.670
Transcripts:
MAP2K3:ENST00000342679.9::
Pathogenicity Data:
Best Score: 0.669612
REMM: 0.670
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-21292722-A-AAGTGCTGGGATTACAGGCATGTGCTAATTTTT [0|1] rs1382066061
Variant score: 0.639
Transcripts:
MAP2K3:ENST00000342679.9:c.50-5691_50-5690insAGTGCTGGGATTACAGGCATGTGCTAATTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.638523
REMM: 0.639
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-21297789-C-CCGG [0/1]
Variant score: 0.584
Transcripts:
MAP2K3:ENST00000342679.9:c.50-624_50-623insCGG:p.(=)
Pathogenicity Data:
Best Score: 0.584088
REMM: 0.584
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-21292719-T-TTAAGTGATCCTTCTGCCTTGGCCTCC [0|1] rs1450347512
Variant score: 0.566
Transcripts:
MAP2K3:ENST00000342679.9:c.50-5694_50-5693insTAAGTGATCCTTCTGCCTTGGCCTCC:p.(=)
Pathogenicity Data:
Best Score: 0.566487
REMM: 0.566
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21306696-T-C [0|1] rs76907177
Variant score: 0.558
Transcripts:
MAP2K3:ENST00000342679.9:c.774+1568T>C:p.(=)
Pathogenicity Data:
Best Score: 0.557974
REMM: 0.558
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21308565-C-T [0/1] rs77000546
Variant score: 0.528
Transcripts:
MAP2K3:ENST00000342679.9:c.774+3437C>T:p.(=)
Pathogenicity Data:
Best Score: 0.528104
REMM: 0.528
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21308724-A-T [0/1] rs76908873
Variant score: 0.514
Transcripts:
MAP2K3:ENST00000342679.9:c.775-3418A>T:p.(=)
Pathogenicity Data:
Best Score: 0.514183
REMM: 0.514
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 17-21334092-G-C [0|1] rs2125157
Variant score: 0.496
Transcripts:
MAP2K3:ENST00000342679.9::
Pathogenicity Data:
Best Score: 0.496339
REMM: 0.496
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 17-21308607-AATT-A [0/1] rs139363444
Variant score: 0.482
Transcripts:
MAP2K3:ENST00000342679.9:c.774+3480_774+3482del:p.(=)
Pathogenicity Data:
Best Score: 0.481954
REMM: 0.482
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-21308155-C-CTTTTTTT [0|1] rs764822853
Variant score: 0.438
Transcripts:
MAP2K3:ENST00000342679.9:c.774+3027_774+3028insTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.439666
REMM: 0.440
Frequency Data:
gnomAD_G_AFR: 0.0089%
gnomAD_G_AMR: 0.0127%
gnomAD_G_EAS: 0.0357%
gnomAD_G_NFE: 0.0079%
INTERGENIC_VARIANT SNV 17-21334078-C-G [0|1] rs2363163
Variant score: 0.411
Transcripts:
MAP2K3:ENST00000342679.9::
Pathogenicity Data:
Best Score: 0.411196
REMM: 0.411
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 17-21333124-ATTTTATTTATTTATTTATTT-A [0/1] rs372721908
Variant score: 0.365
Transcripts:
MAP2K3:ENST00000342679.9::
Pathogenicity Data:
Best Score: 0.36478
REMM: 0.365
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-21297790-T-TGCAGGTGTGGGGAGAGAGCCCGGGACTCGGGACTCTGGCCC [0/1]
Variant score: 0.209
Transcripts:
MAP2K3:ENST00000342679.9:c.50-623_50-622insGCAGGTGTGGGGAGAGAGCCCGGGACTCGGGACTCTGGCCC:p.(=)
Pathogenicity Data:
Best Score: 0.209017
REMM: 0.209
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 17-21333470-AT-A [0/1]
Variant score: 0.167
Transcripts:
MAP2K3:ENST00000342679.9::
Pathogenicity Data:
Best Score: 0.166791
REMM: 0.167
Frequency Data:
No frequency data
INTERGENIC_VARIANT INS 17-21333970-A-ACG [0|1]
Variant score: 0.126
Transcripts:
MAP2K3:ENST00000342679.9::
Pathogenicity Data:
Best Score: 0.125813
REMM: 0.126
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 17-21305619-AGAAGTCC-A [0/1] rs11279112
Variant score: 0.075
Transcripts:
MAP2K3:ENST00000342679.9:c.774+492_774+498del:p.(=)
Pathogenicity Data:
Best Score: 0.0748635
REMM: 0.075
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 17-21329931-C-A [0|1] rs71207228
Variant score: 0.063
Transcripts:
MAP2K3:ENST00000342679.9::
Pathogenicity Data:
Best Score: 0.0633159
REMM: 0.063
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 17-21329939-C-T [0|1]
Variant score: 0.051
Transcripts:
MAP2K3:ENST00000342679.9::
Pathogenicity Data:
Best Score: 0.0507671
REMM: 0.051
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 17-21329908-C-T [0|1] rs71207227
Variant score: 0.037
Transcripts:
MAP2K3:ENST00000342679.9::
Pathogenicity Data:
Best Score: 0.03725
REMM: 0.037
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 17-21333653-C-T [0/1]
Variant score: 0.035
Transcripts:
MAP2K3:ENST00000342679.9::
Pathogenicity Data:
Best Score: 0.0346512
REMM: 0.035
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 17-21329954-A-G [0/1] rs75741373
Variant score: 0.034
Transcripts:
MAP2K3:ENST00000342679.9::
Pathogenicity Data:
Best Score: 0.0336052
REMM: 0.034
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21306314-T-G [0|1] rs79645877
Variant score: 0.023
Transcripts:
MAP2K3:ENST00000342679.9:c.774+1186T>G:p.(=)
Pathogenicity Data:
Best Score: 0.0234861
REMM: 0.023
Frequency Data:
gnomAD_G_AFR: 0.0398%
gnomAD_G_AMR: 0.0609%
gnomAD_G_EAS: 0.1855%
gnomAD_G_NFE: 0.0320%
gnomAD_G_SAS: 0.1245%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21306145-C-T [0/1] rs73313724
Variant score: 0.014
Transcripts:
MAP2K3:ENST00000342679.9:c.774+1017C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0139917
REMM: 0.014
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21304906-C-G [0/1] rs9896302
Variant score: 0.009
Transcripts:
MAP2K3:ENST00000342679.9:c.697-145C>G:p.(=)
Pathogenicity Data:
Best Score: 0.00945794
REMM: 0.009
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21306195-G-T [0/1] rs73313726
Variant score: 0.009
Transcripts:
MAP2K3:ENST00000342679.9:c.774+1067G>T:p.(=)
Pathogenicity Data:
Best Score: 0.00890238
REMM: 0.009
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21306416-G-A [0|1]
Variant score: 0.008
Transcripts:
MAP2K3:ENST00000342679.9:c.774+1288G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00844286
REMM: 0.008
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21306426-A-G [0|1]
Variant score: 0.008
Transcripts:
MAP2K3:ENST00000342679.9:c.774+1298A>G:p.(=)
Pathogenicity Data:
Best Score: 0.00822063
REMM: 0.008
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21306307-G-A [0|1] rs80293992
Variant score: 0.007
Transcripts:
MAP2K3:ENST00000342679.9:c.774+1179G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00706905
REMM: 0.007
Frequency Data:
gnomAD_G_AFR: 0.0460%
gnomAD_G_AMR: 0.0460%
gnomAD_G_EAS: 0.1630%
gnomAD_G_NFE: 0.0220%
gnomAD_G_SAS: 0.0765%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21306071-G-A [0/1] rs73982768
Variant score: 0.007
Transcripts:
MAP2K3:ENST00000342679.9:c.774+943G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00668175
REMM: 0.007
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 17-21329899-T-G [0|1] rs1457794
Variant score: 0.006
Transcripts:
MAP2K3:ENST00000342679.9::
Pathogenicity Data:
Best Score: 0.00590317
REMM: 0.006
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21306218-A-G [0/1] rs60323166
Variant score: 0.006
Transcripts:
MAP2K3:ENST00000342679.9:c.774+1090A>G:p.(=)
Pathogenicity Data:
Best Score: 0.00556508
REMM: 0.006
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21306057-C-T [0/1]
Variant score: 0.005
Transcripts:
MAP2K3:ENST00000342679.9:c.774+929C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00450794
REMM: 0.005
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21306737-A-C [0|1] rs62057740
Variant score: 0.004
Transcripts:
MAP2K3:ENST00000342679.9:c.774+1609A>C:p.(=)
Pathogenicity Data:
Best Score: 0.00400397
REMM: 0.004
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21306727-C-A [0|1]
Variant score: 0.003
Transcripts:
MAP2K3:ENST00000342679.9:c.774+1599C>A:p.(=)
Pathogenicity Data:
Best Score: 0.00322063
REMM: 0.003
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21306255-T-C [0|1]
Variant score: 0.003
Transcripts:
MAP2K3:ENST00000342679.9:c.774+1127T>C:p.(=)
Pathogenicity Data:
Best Score: 0.00250794
REMM: 0.003
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21308823-T-C [0|1] rs5028755
Variant score: 0.002
Transcripts:
MAP2K3:ENST00000342679.9:c.775-3319T>C:p.(=)
Pathogenicity Data:
Best Score: 0.002125
REMM: 0.002
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21306107-C-T [0/1] rs12450529
Variant score: 0.002
Transcripts:
MAP2K3:ENST00000342679.9:c.774+979C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0019381
REMM: 0.002
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21306265-G-C [0|1] rs61297031
Variant score: 0.001
Transcripts:
MAP2K3:ENST00000342679.9:c.774+1137G>C:p.(=)
Pathogenicity Data:
Best Score: 0.00141071
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21308592-T-C [0/1] rs79326150
Variant score: 0.001
Transcripts:
MAP2K3:ENST00000342679.9:c.774+3464T>C:p.(=)
Pathogenicity Data:
Best Score: 0.00133333
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21305570-T-C [0/1]
Variant score: 0.001
Transcripts:
MAP2K3:ENST00000342679.9:c.774+442T>C:p.(=)
Pathogenicity Data:
Best Score: 0.00129524
REMM: 0.001
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 17-21333983-A-G [0/1] rs7224076
Variant score: 0.001
Transcripts:
MAP2K3:ENST00000342679.9::
Pathogenicity Data:
Best Score: 0.0012
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21306729-C-T [0|1] rs62057739
Variant score: 0.001
Transcripts:
MAP2K3:ENST00000342679.9:c.774+1601C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00115397
REMM: 0.001
Frequency Data:
gnomAD_G_AFR: 0.0078%
gnomAD_G_NFE: 0.0015%
INTERGENIC_VARIANT SNV 17-21334942-A-G [0/1] rs1657706
Variant score: 0.001
Transcripts:
MAP2K3:ENST00000342679.9::
Pathogenicity Data:
Best Score: 0.001125
REMM: 0.001
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 17-21320470-T-A [0/1]
Variant score: 0.001
Transcripts:
MAP2K3:ENST00000342679.9::
Pathogenicity Data:
Best Score: 8.0E-4
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21306897-T-C [0|1]
Variant score: 0.001
Transcripts:
MAP2K3:ENST00000342679.9:c.774+1769T>C:p.(=)
Pathogenicity Data:
Best Score: 7.53968E-4
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21308948-T-C [0/1] rs1621446
Variant score: 0.000
Transcripts:
MAP2K3:ENST00000342679.9:c.775-3194T>C:p.(=)
Pathogenicity Data:
Best Score: 4.58333E-4
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21306008-A-G [0|1] rs12452929
Variant score: 0.000
Transcripts:
MAP2K3:ENST00000342679.9:c.774+880A>G:p.(=)
Pathogenicity Data:
Best Score: 4.10714E-4
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21306009-G-A [0|1]
Variant score: 0.000
Transcripts:
MAP2K3:ENST00000342679.9:c.774+881G>A:p.(=)
Pathogenicity Data:
Best Score: 4.10714E-4
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21306741-G-C [0|1] rs62057741
Variant score: 0.000
Transcripts:
MAP2K3:ENST00000342679.9:c.774+1613G>C:p.(=)
Pathogenicity Data:
Best Score: 3.75E-4
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21308822-G-T [0|1] rs5028754
Variant score: 0.000
Transcripts:
MAP2K3:ENST00000342679.9:c.775-3320G>T:p.(=)
Pathogenicity Data:
Best Score: 1.25E-4
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21306691-G-C [0|1]
Variant score: 0.000
Transcripts:
MAP2K3:ENST00000342679.9:c.774+1563G>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21308642-G-C [0/1]
Variant score: 0.000
Transcripts:
MAP2K3:ENST00000342679.9:c.775-3500G>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-21308860-A-G [0/1] rs5028756
Variant score: 0.000
Transcripts:
MAP2K3:ENST00000342679.9:c.775-3282A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data

CDON

Exomiser Score: 0.156 (p=2.2E-1)

Phenotype Score: 0.502

Variant Score: 0.695

Phenotype matches:
Phenotypic similarity 0.471 to Septopreoptic holoprosencephaly associated with CDON.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000772, Abnormal rib morphology
HP:0006625, Multifocal breast carcinoma - HP:0000772, Abnormal rib morphology
Phenotypic similarity 0.330 to mouse mutant involving CDON.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000440, domed cranium
HP:0006625, Multifocal breast carcinoma - MP:0000440, domed cranium
Proximity score 0.502 in interactome to GLI2 and phenotypic similarity 0.676 to Combined pituitary hormone deficiencies, genetic forms associated with GLI2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
HP:0006625, Multifocal breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
Proximity score 0.502 in interactome to GLI2 and phenotypic similarity 0.336 to mouse mutant of GLI2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0004174, abnormal spine curvature
HP:0006625, Multifocal breast carcinoma - MP:0004174, abnormal spine curvature
Proximity score 0.502 in interactome to GLI2 and phenotypic similarity 0.280 to fish mutant of GLI2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0000645, chondrocranium morphology, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0000645, chondrocranium morphology, abnormal
Known diseases:
OMIM:614226 Holoprosencephaly 11 - autosomal dominant
ORPHA:220386 Semilobar holoprosencephaly - polygenic
ORPHA:280195 Septopreoptic holoprosencephaly - polygenic
ORPHA:280200 Microform holoprosencephaly - polygenic
ORPHA:93924 Lobar holoprosencephaly - polygenic
ORPHA:93925 Alobar holoprosencephaly - polygenic
ORPHA:93926 Midline interhemispheric variant of holoprosencephaly - polygenic
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.156 (p=2.2E-1)

Phenotype Score: 0.502

Variant Score: 0.695

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 11-125981970-CTTTTTT-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.695 CONTRIBUTING VARIANT
Transcripts:
CDON:ENST00000531738.6:c.2996-647_2996-642del:p.(=)
Pathogenicity Data:
Best Score: 0.694793
REMM: 0.695
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.002 (p=6.4E-1)

Phenotype Score: 0.251

Variant Score: 0.492

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 11-125981970-CTTTTTT-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.695 CONTRIBUTING VARIANT
Transcripts:
CDON:ENST00000531738.6:c.2996-647_2996-642del:p.(=)
Pathogenicity Data:
Best Score: 0.694793
REMM: 0.695
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 11-125973018-C-CTTTTT [0/1] rs35828939
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.289 CONTRIBUTING VARIANT
Transcripts:
CDON:ENST00000531738.6:c.3356+5285_3356+5286insAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.330071
REMM: 0.330
Frequency Data:
gnomAD_G_AFR: 0.6546%
gnomAD_G_AMR: 0.2616%
gnomAD_G_EAS: 0.0763%
gnomAD_G_NFE: 0.0846%
gnomAD_G_SAS: 0.0537%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 11-125996699-CAA-C [0/1]
Variant score: 0.134
Transcripts:
CDON:ENST00000531738.6:c.2362+506_2362+507del:p.(=)
Pathogenicity Data:
Best Score: 0.134
REMM: 0.134
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 11-125974383-A-AG [0|1]
Variant score: 0.119
Transcripts:
CDON:ENST00000531738.6:c.3356+3920_3356+3921insC:p.(=)
Pathogenicity Data:
Best Score: 0.118814
REMM: 0.119
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 11-125974386-A-AGGGAGGGAGGGAGGGAGGGAGGGAGGGAGGG [0|1]
Variant score: 0.104
Transcripts:
CDON:ENST00000531738.6:c.3356+3917_3356+3918insCCCTCCCTCCCTCCCTCCCTCCCTCCCTCCC:p.(=)
Pathogenicity Data:
Best Score: 0.103888
REMM: 0.104
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 11-125974402-G-GAGGGAGGA [0/1]
Variant score: 0.093
Transcripts:
CDON:ENST00000531738.6:c.3356+3901_3356+3902insTCCTCCCT:p.(=)
Pathogenicity Data:
Best Score: 0.092577
REMM: 0.093
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 11-125971251-C-T [0|1] rs997422538
Variant score: 0.069
Transcripts:
CDON:ENST00000531738.6:c.3356+7053G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0709437
REMM: 0.071
Frequency Data:
gnomAD_G_AFR: 0.0362%
gnomAD_G_AMR: 0.0458%
gnomAD_G_EAS: 0.1939%
gnomAD_G_NFE: 0.0088%
gnomAD_G_SAS: 0.0209%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 11-126041018-G-A [0/1] rs181986657
Variant score: 0.003
Transcripts:
CDON:ENST00000531738.6:c.-61-17481C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00356944
REMM: 0.004
Frequency Data:
gnomAD_G_EAS: 0.1383%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 11-125981744-A-C [0/1] rs183149955
Variant score: 0.001
Transcripts:
CDON:ENST00000531738.6:c.2996-415T>G:p.(=)
Pathogenicity Data:
Best Score: 0.00255238
REMM: 0.003
Frequency Data:
UK10K: 1.4150%
gnomAD_G_AFR: 0.2311%
gnomAD_G_AMR: 0.8771%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.1661%
gnomAD_G_SAS: 0.6642%

NEB

Exomiser Score: 0.155 (p=2.2E-1)

Phenotype Score: 0.514

Variant Score: 0.681

Phenotype matches:
Phenotypic similarity 0.514 to Typical nemaline myopathy associated with NEB.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000774, Narrow chest
HP:0006625, Multifocal breast carcinoma - HP:0000774, Narrow chest
Phenotypic similarity 0.368 to mouse mutant involving NEB.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000160, kyphosis
HP:0006625, Multifocal breast carcinoma - MP:0000160, kyphosis
Proximity score 0.506 in interactome to DES and phenotypic similarity 0.614 to Scapuloperoneal syndrome, neurogenic, Kaeser type associated with DES.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Known diseases:
OMIM:256030 Nemaline myopathy 2, autosomal recessive - autosomal recessive
OMIM:619334 Arthrogryposis multiplex congenita 6 - autosomal recessive
ORPHA:171430 Severe congenital nemaline myopathy - autosomal recessive
ORPHA:171433 Intermediate nemaline myopathy - autosomal recessive
ORPHA:171436 Typical nemaline myopathy - autosomal recessive
ORPHA:171439 Childhood-onset nemaline myopathy - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.155 (p=2.2E-1)

Phenotype Score: 0.514

Variant Score: 0.681

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.514 to ORPHA:171436 Typical nemaline myopathy
Phenotypic similarity 0.504 to ORPHA:171433 Intermediate nemaline myopathy
Phenotypic similarity 0.504 to ORPHA:171439 Childhood-onset nemaline myopathy
Phenotypic similarity 0.496 to ORPHA:171430 Severe congenital nemaline myopathy
Phenotypic similarity 0.484 to OMIM:256030 Nemaline myopathy 2, autosomal recessive
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-151491153-C-T [0/1] rs759274592
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.703 CONTRIBUTING VARIANT
Transcripts:
NEB:ENST00000397345.8:c.25150+530G>A:p.(=)
NEB:ENST00000427231.7:c.25150+530G>A:p.(=)
Pathogenicity Data:
Best Score: 0.709054
REMM: 0.709
Frequency Data:
UK10K: 0.0132%
gnomAD_G_NFE: 0.0059%
gnomAD_G_SAS: 0.0622%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 2-151578276-CGTCAAGTAAAAGGA-C [0|1] rs775966510
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.659 CONTRIBUTING VARIANT
Transcripts:
NEB:ENST00000397345.8:c.16704+1048_16704+1061del:p.(=)
NEB:ENST00000427231.7:c.16704+1048_16704+1061del:p.(=)
Pathogenicity Data:
Best Score: 0.659013
REMM: 0.659
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.015 (p=4.3E-1)

Phenotype Score: 0.253

Variant Score: 0.703

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-151491153-C-T [0/1] rs759274592
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.703 CONTRIBUTING VARIANT
Transcripts:
NEB:ENST00000397345.8:c.25150+530G>A:p.(=)
NEB:ENST00000427231.7:c.25150+530G>A:p.(=)
Pathogenicity Data:
Best Score: 0.709054
REMM: 0.709
Frequency Data:
UK10K: 0.0132%
gnomAD_G_NFE: 0.0059%
gnomAD_G_SAS: 0.0622%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-151578292-A-T [0|1] rs867859040
Variant score: 0.618
Transcripts:
NEB:ENST00000397345.8:c.16704+1046T>A:p.(=)
NEB:ENST00000427231.7:c.16704+1046T>A:p.(=)
Pathogenicity Data:
Best Score: 0.618129
REMM: 0.618
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-151602576-T-C [0/1] rs112260335
ClinVar: BENIGN_OR_LIKELY_BENIGN (CRITERIA_PROVIDED_MULTIPLE_SUBMITTERS_NO_CONFLICTS)
Variant score: 0.517
Transcripts:
NEB:ENST00000397345.8:c.13368+11A>G:p.(=)
NEB:ENST00000427231.7:c.13368+11A>G:p.(=)
Pathogenicity Data:
Best Score: 0.517384
REMM: 0.517
Frequency Data:
No frequency data
MISSENSE_VARIANT SNV 2-151724333-T-C [0/1] rs200719359
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:2, LB:6, B:2)
Variant score: 0.489
Transcripts:
NEB:ENST00000397345.8:c.539A>G:p.(Lys180Arg)
NEB:ENST00000427231.7:c.539A>G:p.(Lys180Arg)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 0.0060%
gnomAD_E_AMR: 0.0359%
gnomAD_E_EAS: 0.0025%
gnomAD_E_NFE: 0.0126%
gnomAD_E_SAS: 0.8605%
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0196%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 0.0250%
gnomAD_G_SAS: 0.8132%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-151602422-T-C [1/1]
Variant score: 0.466
Transcripts:
NEB:ENST00000397345.8:c.13368+165A>G:p.(=)
NEB:ENST00000427231.7:c.13368+165A>G:p.(=)
Pathogenicity Data:
Best Score: 0.465783
REMM: 0.466
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 2-151550266-CA-C [1/1]
Variant score: 0.308
Transcripts:
NEB:ENST00000397345.8:c.19945-527del:p.(=)
NEB:ENST00000427231.7:c.19945-527del:p.(=)
Pathogenicity Data:
Best Score: 0.30771
REMM: 0.308
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 2-151500593-CT-C [0/1] rs11428843
Variant score: 0.205
Transcripts:
NEB:ENST00000397345.8:c.24021+797del:p.(=)
NEB:ENST00000427231.7:c.24021+797del:p.(=)
Pathogenicity Data:
Best Score: 0.242065
REMM: 0.242
Frequency Data:
gnomAD_G_AFR: 0.7518%
gnomAD_G_AMR: 0.0993%
gnomAD_G_EAS: 0.1514%
gnomAD_G_NFE: 0.0523%
gnomAD_G_SAS: 0.2759%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-151602405-T-C [1/1] rs1293265323
Variant score: 0.134
Transcripts:
NEB:ENST00000397345.8:c.13368+182A>G:p.(=)
NEB:ENST00000427231.7:c.13368+182A>G:p.(=)
Pathogenicity Data:
Best Score: 0.134247
REMM: 0.134
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 2-151576516-A-ATTTTTTTTT [0/1]
Variant score: 0.130
Transcripts:
NEB:ENST00000397345.8:c.16705-163_16705-162insAAAAAAAAA:p.(=)
NEB:ENST00000427231.7:c.16705-163_16705-162insAAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.129812
REMM: 0.130
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 2-151576516-AT-A [0/1]
Variant score: 0.130
Transcripts:
NEB:ENST00000397345.8:c.16705-163del:p.(=)
NEB:ENST00000427231.7:c.16705-163del:p.(=)
Pathogenicity Data:
Best Score: 0.129812
REMM: 0.130
Frequency Data:
No frequency data
SYNONYMOUS_VARIANT SNV 2-151666387-C-T [0/1] rs2154179248
ClinVar: LIKELY_BENIGN (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.100
Transcripts:
NEB:ENST00000397345.8:c.4734G>A:p.(=)
NEB:ENST00000427231.7:c.4734G>A:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_NFE: 0.0008%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-151700924-A-G [1/1] rs11900790
Variant score: 0.016
Transcripts:
NEB:ENST00000397345.8:c.1153-3276T>C:p.(=)
NEB:ENST00000427231.7:c.1153-3276T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0162151
REMM: 0.016
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-151703228-T-C [1/1] rs9677191
Variant score: 0.007
Transcripts:
NEB:ENST00000397345.8:c.1152+3653A>G:p.(=)
NEB:ENST00000427231.7:c.1152+3653A>G:p.(=)
Pathogenicity Data:
Best Score: 0.00697778
REMM: 0.007
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-151699988-T-C [0/1]
Variant score: 0.005
Transcripts:
NEB:ENST00000397345.8:c.1153-2340A>G:p.(=)
NEB:ENST00000427231.7:c.1153-2340A>G:p.(=)
Pathogenicity Data:
Best Score: 0.00545833
REMM: 0.005
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-151701178-T-C [1/1] rs200915868
Variant score: 0.005
Transcripts:
NEB:ENST00000397345.8:c.1153-3530A>G:p.(=)
NEB:ENST00000427231.7:c.1153-3530A>G:p.(=)
Pathogenicity Data:
Best Score: 0.00488056
REMM: 0.005
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-151703592-T-C [1/1]
Variant score: 0.004
Transcripts:
NEB:ENST00000397345.8:c.1152+3289A>G:p.(=)
NEB:ENST00000427231.7:c.1152+3289A>G:p.(=)
Pathogenicity Data:
Best Score: 0.00380317
REMM: 0.004
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-151703501-C-G [1/1] rs28827472
Variant score: 0.003
Transcripts:
NEB:ENST00000397345.8:c.1152+3380G>C:p.(=)
NEB:ENST00000427231.7:c.1152+3380G>C:p.(=)
Pathogenicity Data:
Best Score: 0.00308889
REMM: 0.003
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 2-151689197-CT-C [1/1] rs11305294
Variant score: 0.000
Transcripts:
NEB:ENST00000397345.8:c.2311-802del:p.(=)
NEB:ENST00000427231.7:c.2311-802del:p.(=)
Pathogenicity Data:
Best Score: 4.58333E-4
REMM: 0.000
Frequency Data:
No frequency data

IQSEC3

Exomiser Score: 0.155 (p=2.2E-1)

Phenotype Score: 0.502

Variant Score: 0.694

Phenotype matches:
Phenotypic similarity 0.321 to mouse mutant involving IQSEC3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0010124, decreased bone mineral content
HP:0006625, Multifocal breast carcinoma - MP:0010124, decreased bone mineral content
Proximity score 0.502 in interactome to DCC and phenotypic similarity 0.620 to Kallmann syndrome associated with DCC.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003187, Breast hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0003187, Breast hypoplasia
Proximity score 0.502 in interactome to DCC and phenotypic similarity 0.268 to mouse mutant of DCC.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002417, abnormal megakaryocyte morphology
HP:0006625, Multifocal breast carcinoma - MP:0002417, abnormal megakaryocyte morphology
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.155 (p=2.2E-1)

Phenotype Score: 0.502

Variant Score: 0.694

No phenotype matches to diseases with this MOI.
Variants contributing to score:
INTERGENIC_VARIANT DEL 12-55472-GT-G [0/1] rs5795907
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.694 CONTRIBUTING VARIANT
Transcripts:
IQSEC3:ENST00000538872.6::
Pathogenicity Data:
Best Score: 0.694393
REMM: 0.694
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.112 (p=2.5E-1)

Phenotype Score: 0.502

Variant Score: 0.653

No phenotype matches to diseases with this MOI.
Variants contributing to score:
INTERGENIC_VARIANT DEL 12-55472-GT-G [0/1] rs5795907
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.694 CONTRIBUTING VARIANT
Transcripts:
IQSEC3:ENST00000538872.6::
Pathogenicity Data:
Best Score: 0.694393
REMM: 0.694
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 12-51145-G-C [0/1] rs7296590
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.613 CONTRIBUTING VARIANT
Transcripts:
IQSEC3:ENST00000538872.6::
Pathogenicity Data:
Best Score: 0.612549
REMM: 0.613
Frequency Data:
No frequency data
Other passed variants:
INTERGENIC_VARIANT SNV 12-186746-G-A [0/1] rs538399904
Variant score: 0.534
Transcripts:
IQSEC3:ENST00000538872.6::
Pathogenicity Data:
Best Score: 0.542313
REMM: 0.542
Frequency Data:
gnomAD_G_AFR: 0.0024%
gnomAD_G_SAS: 0.1039%
FIVE_PRIME_UTR_EXON_VARIANT SNV 12-66802-G-C [0/1] rs1449690925
Variant score: 0.530
Transcripts:
IQSEC3:ENST00000538872.6:c.-81G>C:p.(=)
Pathogenicity Data:
Best Score: 0.530467
REMM: 0.530
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-96260-G-A [0/1]
Variant score: 0.445
Transcripts:
IQSEC3:ENST00000538872.6:c.555-2886G>A:p.(=)
Pathogenicity Data:
Best Score: 0.444923
REMM: 0.445
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-73049-TATAAATAAATAAATAA-T [0/1] rs58047522
Variant score: 0.336
Transcripts:
IQSEC3:ENST00000538872.6:c.554+5614_554+5629del:p.(=)
Pathogenicity Data:
Best Score: 0.335652
REMM: 0.336
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-77915-C-T [0/1] rs2650199
Variant score: 0.328
Transcripts:
IQSEC3:ENST00000538872.6:c.554+10479C>T:p.(=)
Pathogenicity Data:
Best Score: 0.70203
REMM: 0.702
Frequency Data:
gnomAD_G_AFR: 0.2738%
gnomAD_G_AMR: 0.5709%
gnomAD_G_EAS: 0.0395%
gnomAD_G_NFE: 1.5964%
gnomAD_G_SAS: 0.5537%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-163375-TC-T [0/1] rs36125147
Variant score: 0.310
Transcripts:
IQSEC3:ENST00000538872.6:c.2584-118del:p.(=)
Pathogenicity Data:
Best Score: 0.330065
REMM: 0.330
Frequency Data:
gnomAD_G_AFR: 0.3774%
gnomAD_G_AMR: 0.1477%
gnomAD_G_EAS: 0.3030%
gnomAD_G_NFE: 0.2876%
UPSTREAM_GENE_VARIANT SNV 12-63107-G-A [0/1]
Variant score: 0.306
Transcripts:
IQSEC3:ENST00000538872.6::
Pathogenicity Data:
Best Score: 0.30569
REMM: 0.306
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-77606-G-A [0/1] rs61908583
Variant score: 0.225
Transcripts:
IQSEC3:ENST00000538872.6:c.554+10170G>A:p.(=)
Pathogenicity Data:
Best Score: 0.225482
REMM: 0.225
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT SNV 12-63006-A-G [0/1]
Variant score: 0.220
Transcripts:
IQSEC3:ENST00000538872.6::
Pathogenicity Data:
Best Score: 0.219637
REMM: 0.220
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-163369-CCT-C [0/1] rs373373512
Variant score: 0.210
Transcripts:
IQSEC3:ENST00000538872.6:c.2584-124_2584-123del:p.(=)
Pathogenicity Data:
Best Score: 0.227553
REMM: 0.228
Frequency Data:
gnomAD_G_AFR: 0.3091%
gnomAD_G_AMR: 0.1944%
gnomAD_G_EAS: 0.3650%
gnomAD_G_NFE: 0.4558%
INTERGENIC_VARIANT SNV 12-55748-T-C [0|1] rs77716916
Variant score: 0.170
Transcripts:
IQSEC3:ENST00000538872.6::
Pathogenicity Data:
Best Score: 0.169816
REMM: 0.170
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT INS 12-62768-G-GAGAA [0/1]
Variant score: 0.161
Transcripts:
IQSEC3:ENST00000538872.6::
Pathogenicity Data:
Best Score: 0.161307
REMM: 0.161
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 12-55804-A-G [0/1] rs7972024
Variant score: 0.156
Transcripts:
IQSEC3:ENST00000538872.6::
Pathogenicity Data:
Best Score: 0.155727
REMM: 0.156
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 12-55727-C-T [0|1] rs73032178
Variant score: 0.141
Transcripts:
IQSEC3:ENST00000538872.6::
Pathogenicity Data:
Best Score: 0.14052
REMM: 0.141
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-103852-T-G [1|1]
Variant score: 0.128
Transcripts:
IQSEC3:ENST00000538872.6:c.623+4638T>G:p.(=)
Pathogenicity Data:
Best Score: 0.12809
REMM: 0.128
Frequency Data:
No frequency data
INTERGENIC_VARIANT INS 12-55700-G-GCCTTGGCCTCCCAAAGT [0|1] rs1375643245
Variant score: 0.099
Transcripts:
IQSEC3:ENST00000538872.6::
Pathogenicity Data:
Best Score: 0.0993865
REMM: 0.099
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-103802-C-G [1/1]
Variant score: 0.087
Transcripts:
IQSEC3:ENST00000538872.6:c.623+4588C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0873758
REMM: 0.087
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-163367-C-G [0/1] rs112602274
Variant score: 0.087
Transcripts:
IQSEC3:ENST00000538872.6:c.2584-127C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0928821
REMM: 0.093
Frequency Data:
gnomAD_G_AFR: 0.2715%
gnomAD_G_AMR: 0.1775%
gnomAD_G_EAS: 0.3236%
gnomAD_G_NFE: 0.3715%
INTERGENIC_VARIANT SNV 12-55775-G-A [0/1] rs7953506
Variant score: 0.051
Transcripts:
IQSEC3:ENST00000538872.6::
Pathogenicity Data:
Best Score: 0.0511028
REMM: 0.051
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 12-55715-T-C [0|1] rs77523372
Variant score: 0.035
Transcripts:
IQSEC3:ENST00000538872.6::
Pathogenicity Data:
Best Score: 0.0354698
REMM: 0.035
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT SNV 12-64763-G-C [0/1] rs2760723
Variant score: 0.035
Transcripts:
IQSEC3:ENST00000538872.6::
Pathogenicity Data:
Best Score: 0.0351948
REMM: 0.035
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 12-51426-A-G [0/1] rs7316906
Variant score: 0.001
Transcripts:
IQSEC3:ENST00000538872.6::
Pathogenicity Data:
Best Score: 0.00128571
REMM: 0.001
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT SNV 12-62801-T-C [0/1]
Variant score: 0.001
Transcripts:
IQSEC3:ENST00000538872.6::
Pathogenicity Data:
Best Score: 0.00116667
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-151049-C-T [1/1]
Variant score: 0.001
Transcripts:
IQSEC3:ENST00000538872.6:c.2154-5976C>T:p.(=)
Pathogenicity Data:
Best Score: 6.98413E-4
REMM: 0.001
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT SNV 12-62586-A-G [0/1]
Variant score: 0.000
Transcripts:
IQSEC3:ENST00000538872.6::
Pathogenicity Data:
Best Score: 2.85714E-4
REMM: 0.000
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT SNV 12-62886-T-C [0/1]
Variant score: 0.000
Transcripts:
IQSEC3:ENST00000538872.6::
Pathogenicity Data:
Best Score: 2.85714E-4
REMM: 0.000
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 12-49980-C-T [0/1] rs7342325
Variant score: 0.000
Transcripts:
IQSEC3:ENST00000538872.6::
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 12-60861-T-C [0/1] rs4116030
Variant score: 0.000
Transcripts:
IQSEC3:ENST00000538872.6::
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-72274-C-T [0/1] rs2760695
Variant score: 0.000
Transcripts:
IQSEC3:ENST00000538872.6:c.554+4838C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-72364-A-G [0/1] rs2760693
Variant score: 0.000
Transcripts:
IQSEC3:ENST00000538872.6:c.554+4928A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-73040-T-C [1/1] rs3864936
Variant score: 0.000
Transcripts:
IQSEC3:ENST00000538872.6:c.554+5604T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data

NEDD4L

Exomiser Score: 0.152 (p=2.3E-1)

Phenotype Score: 0.503

Variant Score: 0.690

Phenotype matches:
Phenotypic similarity 0.425 to Periventricular nodular heterotopia associated with NEDD4L.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003834, Shoulder dislocation
HP:0006625, Multifocal breast carcinoma - HP:0003834, Shoulder dislocation
Proximity score 0.503 in interactome to TGFBR2 and phenotypic similarity 0.998 to Lynch syndrome associated with TGFBR2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.503 in interactome to TGFBR2 and phenotypic similarity 0.368 to mouse mutant of TGFBR2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000160, kyphosis
HP:0006625, Multifocal breast carcinoma - MP:0000160, kyphosis
Known diseases:
OMIM:617201 Periventricular nodular heterotopia 7 - autosomal dominant
ORPHA:98892 Periventricular nodular heterotopia - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.152 (p=2.3E-1)

Phenotype Score: 0.503

Variant Score: 0.690

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.425 to ORPHA:98892 Periventricular nodular heterotopia
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 18-58282160-A-G [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.690 CONTRIBUTING VARIANT
Transcripts:
NEDD4L:ENST00000400345.8:c.297+30106A>G:p.(=)
Pathogenicity Data:
Best Score: 0.690054
REMM: 0.690
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.011 (p=4.6E-1)

Phenotype Score: 0.251

Variant Score: 0.673

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 18-58282160-A-G [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.690 CONTRIBUTING VARIANT
Transcripts:
NEDD4L:ENST00000400345.8:c.297+30106A>G:p.(=)
Pathogenicity Data:
Best Score: 0.690054
REMM: 0.690
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 18-58245674-CT-C [0/1] rs57282316
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.656 CONTRIBUTING VARIANT
Transcripts:
NEDD4L:ENST00000400345.8:c.204+167del:p.(=)
Pathogenicity Data:
Best Score: 0.655932
REMM: 0.656
Frequency Data:
No frequency data
Other passed variants:
MISSENSE_VARIANT SNV 18-58044688-T-A [0/1] rs1185203471
Variant score: 0.600
Transcripts:
NEDD4L:ENST00000400345.8:c.28T>A:p.(Tyr10Asn)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_NFE: 0.0003%
gnomAD_E_SAS: 0.0012%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 18-58260628-G-C [0/1]
Variant score: 0.551
Transcripts:
NEDD4L:ENST00000400345.8:c.297+8574G>C:p.(=)
Pathogenicity Data:
Best Score: 0.551371
REMM: 0.551
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 18-58276187-CTTTTTCGTTTTTTTTT-C [0|1] rs776461305
Variant score: 0.542
Transcripts:
NEDD4L:ENST00000400345.8:c.297+24134_297+24149del:p.(=)
Pathogenicity Data:
Best Score: 0.542004
REMM: 0.542
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT SNV 18-58040173-C-T [0/1] rs183836846
Variant score: 0.517
Transcripts:
NEDD4L:ENST00000400345.8::
Pathogenicity Data:
Best Score: 0.521063
REMM: 0.521
Frequency Data:
gnomAD_G_AFR: 0.0096%
gnomAD_G_AMR: 0.0589%
gnomAD_G_NFE: 0.0441%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 18-58377834-CCTA-C [0/1] rs571832038
Variant score: 0.493
Transcripts:
NEDD4L:ENST00000400345.8:c.2352+4566_2352+4568del:p.(=)
Pathogenicity Data:
Best Score: 0.557976
REMM: 0.558
Frequency Data:
UK10K: 0.2380%
gnomAD_G_AFR: 0.0289%
gnomAD_G_AMR: 0.6208%
gnomAD_G_NFE: 0.3395%
gnomAD_G_SAS: 0.1449%
CODING_TRANSCRIPT_INTRON_VARIANT INS 18-58056894-C-CTTTTTT [0/1] rs74183230
Variant score: 0.452
Transcripts:
NEDD4L:ENST00000400345.8:c.48+12186_48+12187insTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.452368
REMM: 0.452
Frequency Data:
No frequency data
THREE_PRIME_UTR_EXON_VARIANT DEL 18-58398157-TA-T [0/1]
Variant score: 0.351
Transcripts:
NEDD4L:ENST00000400345.8:c.*1925del:p.(=)
Pathogenicity Data:
Best Score: 0.350662
REMM: 0.351
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 18-58037736-G-A [0/1] rs139381892
Variant score: 0.275
Transcripts:
NEDD4L:ENST00000400345.8::
Pathogenicity Data:
Best Score: 0.456514
REMM: 0.457
Frequency Data:
UK10K: 0.5686%
gnomAD_G_AFR: 0.1084%
gnomAD_G_AMR: 0.8240%
gnomAD_G_EAS: 0.0386%
gnomAD_G_NFE: 0.6086%
gnomAD_G_SAS: 1.3699%
CODING_TRANSCRIPT_INTRON_VARIANT INS 18-58082102-A-ATATATATATTTTTTTT [0/1]
Variant score: 0.237
Transcripts:
NEDD4L:ENST00000400345.8:c.48+37394_48+37395insTATATATATTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.236632
REMM: 0.237
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 18-58209240-T-C [1/1] rs118076950
Variant score: 0.142
Transcripts:
NEDD4L:ENST00000400345.8:c.123-36187T>C:p.(=)
Pathogenicity Data:
Best Score: 0.142303
REMM: 0.142
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 18-58062987-CA-C [0|1]
Variant score: 0.135
Transcripts:
NEDD4L:ENST00000400345.8:c.48+18280del:p.(=)
Pathogenicity Data:
Best Score: 0.135361
REMM: 0.135
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 18-58224433-G-C [0/1] rs573611696
Variant score: 0.129
Transcripts:
NEDD4L:ENST00000400345.8:c.123-20994G>C:p.(=)
Pathogenicity Data:
Best Score: 0.139459
REMM: 0.139
Frequency Data:
UK10K: 0.2777%
gnomAD_G_AFR: 0.0938%
gnomAD_G_AMR: 0.1308%
gnomAD_G_NFE: 0.4395%
CODING_TRANSCRIPT_INTRON_VARIANT INS 18-58347214-G-GC [0/1] rs1293604264
Variant score: 0.119
Transcripts:
NEDD4L:ENST00000400345.8:c.1576-2323_1576-2322insC:p.(=)
Pathogenicity Data:
Best Score: 0.19597
REMM: 0.196
Frequency Data:
gnomAD_G_AFR: 0.0717%
gnomAD_G_AMR: 0.1082%
gnomAD_G_EAS: 0.1319%
gnomAD_G_NFE: 0.2476%
gnomAD_G_SAS: 1.3624%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 18-58084671-TTGTG-T [0/1]
Variant score: 0.108
Transcripts:
NEDD4L:ENST00000400345.8:c.48+39964_48+39967del:p.(=)
Pathogenicity Data:
Best Score: 0.108067
REMM: 0.108
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 18-58322916-A-G [0/1]
Variant score: 0.102
Transcripts:
NEDD4L:ENST00000400345.8:c.411-316A>G:p.(=)
Pathogenicity Data:
Best Score: 0.101648
REMM: 0.102
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 18-58035038-T-G [0/1] rs113900503
Variant score: 0.100
Transcripts:
NEDD4L:ENST00000400345.8::
Pathogenicity Data:
Best Score: 0.54728
REMM: 0.547
Frequency Data:
UK10K: 1.2563%
gnomAD_G_AFR: 0.2190%
gnomAD_G_AMR: 0.8434%
gnomAD_G_EAS: 0.0963%
gnomAD_G_NFE: 1.4494%
gnomAD_G_SAS: 1.9510%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 18-58059394-C-A [0/1] rs187455961
Variant score: 0.062
Transcripts:
NEDD4L:ENST00000400345.8:c.48+14686C>A:p.(=)
Pathogenicity Data:
Best Score: 0.0639425
REMM: 0.064
Frequency Data:
UK10K: 0.0793%
gnomAD_G_AFR: 0.0164%
gnomAD_G_AMR: 0.1192%
gnomAD_G_EAS: 0.0386%
gnomAD_G_NFE: 0.1692%
gnomAD_G_SAS: 0.0831%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 18-58209213-A-T [1/1]
Variant score: 0.025
Transcripts:
NEDD4L:ENST00000400345.8:c.123-36214A>T:p.(=)
Pathogenicity Data:
Best Score: 0.0248063
REMM: 0.025
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 18-58129989-G-T [0/1] rs902451715
Variant score: 0.020
Transcripts:
NEDD4L:ENST00000400345.8:c.49-35799G>T:p.(=)
Pathogenicity Data:
Best Score: 0.0196202
REMM: 0.020
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 18-58338170-A-G [0/1] rs191648700
Variant score: 0.007
Transcripts:
NEDD4L:ENST00000400345.8:c.1125+2633A>G:p.(=)
Pathogenicity Data:
Best Score: 0.00769841
REMM: 0.008
Frequency Data:
UK10K: 0.2248%
gnomAD_G_AFR: 0.0361%
gnomAD_G_AMR: 0.6665%
gnomAD_G_NFE: 0.3645%
gnomAD_G_SAS: 0.1036%
CODING_TRANSCRIPT_INTRON_VARIANT INS 18-58138324-T-TTCTTCCCTCCCCTCCTCCTCTTCCCTCCCCTCCTCC [1/1] rs751189848
Variant score: 0.003
Transcripts:
NEDD4L:ENST00000400345.8:c.49-27464_49-27463insTCTTCCCTCCCCTCCTCCTCTTCCCTCCCCTCCTCC:p.(=)
Pathogenicity Data:
Best Score: 0.0029
REMM: 0.003
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 18-58176902-G-A [0/1] rs562891546
Variant score: 0.003
Transcripts:
NEDD4L:ENST00000400345.8:c.122+11041G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00288611
REMM: 0.003
Frequency Data:
UK10K: 0.0397%
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0523%
gnomAD_G_NFE: 0.0529%
gnomAD_G_SAS: 0.3934%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 18-58105489-C-T [0/1] rs117371575
Variant score: 0.002
Transcripts:
NEDD4L:ENST00000400345.8:c.49-60299C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0061119
REMM: 0.006
Frequency Data:
UK10K: 0.8199%
gnomAD_G_AFR: 0.1348%
gnomAD_G_AMR: 0.9809%
gnomAD_G_EAS: 0.0771%
gnomAD_G_NFE: 0.8279%
gnomAD_G_SAS: 1.7464%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 18-58178555-G-A [0/1] rs140436267
Variant score: 0.001
Transcripts:
NEDD4L:ENST00000400345.8:c.122+12694G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00137778
REMM: 0.001
Frequency Data:
UK10K: 0.0529%
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0523%
gnomAD_G_EAS: 0.2119%
gnomAD_G_NFE: 0.0588%
gnomAD_G_SAS: 0.4148%
CODING_TRANSCRIPT_INTRON_VARIANT INS 18-58276215-G-GGC [0|1]
Variant score: 0.001
Transcripts:
NEDD4L:ENST00000400345.8:c.297+24161_297+24162insGC:p.(=)
Pathogenicity Data:
Best Score: 0.001125
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 18-58276216-T-G [0|1]
Variant score: 0.001
Transcripts:
NEDD4L:ENST00000400345.8:c.297+24162T>G:p.(=)
Pathogenicity Data:
Best Score: 0.001125
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 18-58126065-C-T [0/1] rs186828871
Variant score: 0.001
Transcripts:
NEDD4L:ENST00000400345.8:c.49-39723C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00111111
REMM: 0.001
Frequency Data:
UK10K: 0.4628%
gnomAD_G_AFR: 0.0361%
gnomAD_G_AMR: 0.0915%
gnomAD_G_NFE: 0.3543%
gnomAD_G_SAS: 0.0622%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 18-58159230-T-A [0/1] rs557599120
Variant score: 0.000
Transcripts:
NEDD4L:ENST00000400345.8:c.49-6558T>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0097%
gnomAD_G_AMR: 0.0524%
gnomAD_G_NFE: 0.0603%
gnomAD_G_SAS: 0.4170%
CODING_TRANSCRIPT_INTRON_VARIANT INS 18-58348326-C-CTTTTTTTT [0/1] rs771263533
Variant score: 0.000
Transcripts:
NEDD4L:ENST00000400345.8:c.1576-1211_1576-1210insTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data

VLDLR

Exomiser Score: 0.150 (p=2.3E-1)

Phenotype Score: 0.502

Variant Score: 0.690

Phenotype matches:
Proximity score 0.502 in interactome to ITGA3 and phenotypic similarity 0.603 to Epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome associated with ITGA3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Known diseases:
OMIM:224050 Cerebellar hypoplasia, impaired intellectual development, and dysequilibrium syndrome 1 - autosomal recessive
ORPHA:1766 Dysequilibrium syndrome - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.150 (p=2.3E-1)

Phenotype Score: 0.502

Variant Score: 0.690

No phenotype matches to diseases with this MOI.
Variants contributing to score:
THREE_PRIME_UTR_EXON_VARIANT DEL 9-2656942-CA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.690 CONTRIBUTING VARIANT
Transcripts:
VLDLR:ENST00000382100.8:c.*3102del:p.(=)
Pathogenicity Data:
Best Score: 0.690249
REMM: 0.690
Frequency Data:
No frequency data
THREE_PRIME_UTR_EXON_VARIANT DEL 9-2656942-CAAAA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.690 CONTRIBUTING VARIANT
Transcripts:
VLDLR:ENST00000382100.8:c.*3099_*3102del:p.(=)
Pathogenicity Data:
Best Score: 0.690249
REMM: 0.690
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.013 (p=4.4E-1)

Phenotype Score: 0.251

Variant Score: 0.690

No phenotype matches to diseases with this MOI.
Variants contributing to score:
THREE_PRIME_UTR_EXON_VARIANT DEL 9-2656942-CA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.690 CONTRIBUTING VARIANT
Transcripts:
VLDLR:ENST00000382100.8:c.*3102del:p.(=)
Pathogenicity Data:
Best Score: 0.690249
REMM: 0.690
Frequency Data:
No frequency data
Other passed variants:
MISSENSE_VARIANT SNV 9-2643727-C-T [0/1] rs149772780
Variant score: 0.600
Transcripts:
VLDLR:ENST00000382100.8:c.920C>T:p.(Ser307Phe)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_EAS: 0.0025%
CODING_TRANSCRIPT_INTRON_VARIANT INS 9-2644325-A-ATTTT [0/1] rs374242751
Variant score: 0.262
Transcripts:
VLDLR:ENST00000382100.8:c.1066+366_1066+367insTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.261677
REMM: 0.262
Frequency Data:
No frequency data

AKAP10

Exomiser Score: 0.148 (p=2.3E-1)

Phenotype Score: 0.501

Variant Score: 0.689

Phenotype matches:
Proximity score 0.501 in interactome to PRKAR1A and phenotypic similarity 0.915 to Carney complex associated with PRKAR1A.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0100013, Neoplasm of the breast
HP:0006625, Multifocal breast carcinoma - HP:0100013, Neoplasm of the breast
Proximity score 0.501 in interactome to PRKAR1A and phenotypic similarity 0.332 to mouse mutant of PRKAR1A.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002116, abnormal craniofacial bone morphology
HP:0006625, Multifocal breast carcinoma - MP:0002116, abnormal craniofacial bone morphology
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.148 (p=2.3E-1)

Phenotype Score: 0.501

Variant Score: 0.689

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 17-19920855-CAAAAA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.689 CONTRIBUTING VARIANT
Transcripts:
AKAP10:ENST00000225737.11:c.1752-742_1752-738del:p.(=)
Pathogenicity Data:
Best Score: 0.688814
REMM: 0.689
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.052 (p=3.2E-1)

Phenotype Score: 0.501

Variant Score: 0.563

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 17-19920855-CAAAAA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.689 CONTRIBUTING VARIANT
Transcripts:
AKAP10:ENST00000225737.11:c.1752-742_1752-738del:p.(=)
Pathogenicity Data:
Best Score: 0.688814
REMM: 0.689
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-19910325-C-CAAAAAAAAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.438 CONTRIBUTING VARIANT
Transcripts:
AKAP10:ENST00000225737.11:c.1835-348_1835-347insTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.438171
REMM: 0.438
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-19969984-A-G [0/1] rs150778089
Variant score: 0.392
Transcripts:
AKAP10:ENST00000225737.11:c.89-1523T>C:p.(=)
Pathogenicity Data:
Best Score: 0.710169
REMM: 0.710
Frequency Data:
UK10K: 1.4282%
gnomAD_G_AFR: 0.2215%
gnomAD_G_AMR: 1.4450%
gnomAD_G_NFE: 1.4620%
gnomAD_G_SAS: 0.1864%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 17-19911835-CAAAAAAAA-C [0/1]
Variant score: 0.174
Transcripts:
AKAP10:ENST00000225737.11:c.1835-1865_1835-1858del:p.(=)
Pathogenicity Data:
Best Score: 0.17433
REMM: 0.174
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 17-19946236-ATTATATAT-A [0/1] rs1172320598
Variant score: 0.170
Transcripts:
AKAP10:ENST00000225737.11:c.976+1163_976+1170del:p.(=)
Pathogenicity Data:
Best Score: 0.169565
REMM: 0.170
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 17-19946239-A-AT [0/1] rs1567765519
Variant score: 0.126
Transcripts:
AKAP10:ENST00000225737.11:c.976+1167_976+1168insA:p.(=)
Pathogenicity Data:
Best Score: 0.148175
REMM: 0.148
Frequency Data:
gnomAD_G_EAS: 0.7407%
gnomAD_G_NFE: 0.1037%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 17-19931610-C-T [0/1] rs181639293
Variant score: 0.000
Transcripts:
AKAP10:ENST00000225737.11:c.1641+195G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.0844%
gnomAD_G_AFR: 0.1760%
gnomAD_G_AMR: 0.6482%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.7664%
gnomAD_G_SAS: 0.0831%

PIGW

Exomiser Score: 0.147 (p=2.3E-1)

Phenotype Score: 0.587

Variant Score: 0.591

Phenotype matches:
Phenotypic similarity 0.587 to Hyperphosphatasia-intellectual disability syndrome associated with PIGW.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0002558, Supernumerary nipple
HP:0006625, Multifocal breast carcinoma - HP:0002558, Supernumerary nipple
Proximity score 0.501 in interactome to PIGN and phenotypic similarity 0.613 to Fryns syndrome associated with PIGN.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0006709, Aplasia/Hypoplasia of the nipples
HP:0006625, Multifocal breast carcinoma - HP:0006709, Aplasia/Hypoplasia of the nipples
Proximity score 0.501 in interactome to PIGN and phenotypic similarity 0.334 to mouse mutant of PIGN.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0004384, small interparietal bone
HP:0006625, Multifocal breast carcinoma - MP:0004384, small interparietal bone
Known diseases:
OMIM:616025 Glycosylphosphatidylinositol biosynthesis defect 11 - autosomal recessive
ORPHA:247262 Hyperphosphatasia-intellectual disability syndrome - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.147 (p=2.3E-1)

Phenotype Score: 0.587

Variant Score: 0.591

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.587 to ORPHA:247262 Hyperphosphatasia-intellectual disability syndrome
Variants contributing to score:
DISRUPTIVE_INFRAME_DELETION DEL 17-36537706-CATT-C [0/1] rs2074161776
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.850 CONTRIBUTING VARIANT
Transcripts:
PIGW:ENST00000614443.2:c.606_608del:p.(Leu203del)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_NFE: 0.0004%
FIVE_PRIME_UTR_INTRON_VARIANT INS 17-36536524-C-CTT [0/1] rs10715370
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.332 CONTRIBUTING VARIANT
Transcripts:
PIGW:ENST00000614443.2:c.-8-570_-8-569insTT:p.(=)
Pathogenicity Data:
Best Score: 0.332367
REMM: 0.332
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.053 (p=3.2E-1)

Phenotype Score: 0.250

Variant Score: 0.850

No phenotype matches to diseases with this MOI.
Variants contributing to score:
DISRUPTIVE_INFRAME_DELETION DEL 17-36537706-CATT-C [0/1] rs2074161776
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.850 CONTRIBUTING VARIANT
Transcripts:
PIGW:ENST00000614443.2:c.606_608del:p.(Leu203del)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_NFE: 0.0004%

ALG9

Exomiser Score: 0.145 (p=2.3E-1)

Phenotype Score: 0.635

Variant Score: 0.534

Phenotype matches:
Phenotypic similarity 0.635 to Congenital disorder of glycosylation, type Il associated with ALG9.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Proximity score 0.509 in interactome to ALG12 and phenotypic similarity 0.643 to ALG12-CDG associated with ALG12.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Known diseases:
OMIM:263210 Gillessen-Kaesbach-Nishimura syndrome - autosomal recessive
OMIM:608776 Congenital disorder of glycosylation, type Il - autosomal recessive
ORPHA:730 Autosomal dominant polycystic kidney disease - autosomal dominant
ORPHA:79328 ALG9-CDG - autosomal recessive
ORPHA:79328 ALG9-CDG - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.145 (p=2.3E-1)

Phenotype Score: 0.635

Variant Score: 0.534

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.635 to OMIM:608776 Congenital disorder of glycosylation, type Il
Phenotypic similarity 0.635 to ORPHA:79328 ALG9-CDG
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 11-111854263-AT-A [0/1] rs34277511
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting, PP4]
Variant score: 0.569 CONTRIBUTING VARIANT
Transcripts:
ALG9:ENST00000616540.5:c.702-528del:p.(=)
Pathogenicity Data:
Best Score: 0.569392
REMM: 0.569
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 11-111854685-T-C [0/1] rs187455379
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PP4]
Variant score: 0.499 CONTRIBUTING VARIANT
Transcripts:
ALG9:ENST00000616540.5:c.702-949A>G:p.(=)
Pathogenicity Data:
Best Score: 0.534548
REMM: 0.535
Frequency Data:
UK10K: 0.0264%
gnomAD_G_AFR: 0.0240%
gnomAD_G_AMR: 0.3985%
gnomAD_G_NFE: 0.0897%
gnomAD_G_SAS: 0.0414%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.059 (p=3.1E-1)

Phenotype Score: 0.509

Variant Score: 0.569

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 11-111854263-AT-A [0/1] rs34277511
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.569 CONTRIBUTING VARIANT
Transcripts:
ALG9:ENST00000616540.5:c.702-528del:p.(=)
Pathogenicity Data:
Best Score: 0.569392
REMM: 0.569
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 11-111870387-A-C [0|1] rs782169051
ClinVar: BENIGN (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.390
Transcripts:
ALG9:ENST00000616540.5:c.132-17T>G:p.(=)
Pathogenicity Data:
Best Score: 0.760319
REMM: 0.760
Frequency Data:
gnomAD_E_AFR: 0.3230%
gnomAD_E_AMR: 0.8497%
gnomAD_E_EAS: 0.1325%
gnomAD_E_NFE: 1.3185%
gnomAD_E_SAS: 0.3157%
gnomAD_G_AFR: 0.2160%
gnomAD_G_AMR: 1.1721%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 1.5268%
gnomAD_G_SAS: 0.3970%

GCH1

Exomiser Score: 0.144 (p=2.3E-1)

Phenotype Score: 0.502

Variant Score: 0.685

Phenotype matches:
Proximity score 0.502 in interactome to POLR3H and phenotypic similarity 0.676 to 46,XX gonadal dysgenesis associated with POLR3H.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
HP:0006625, Multifocal breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
Known diseases:
OMIM:128230 Dystonia, DOPA-responsive - autosomal dominant/recessive
OMIM:233910 Hyperphenylalaninemia, BH4-deficient, B - autosomal recessive
ORPHA:98808 Autosomal dominant dopa-responsive dystonia - autosomal dominant/recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.144 (p=2.3E-1)

Phenotype Score: 0.502

Variant Score: 0.685

No phenotype matches to diseases with this MOI.
Variants contributing to score:
DOWNSTREAM_GENE_VARIANT DEL 14-54838219-CA-C [1/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.685 CONTRIBUTING VARIANT
Transcripts:
GCH1:ENST00000491895.7::
Pathogenicity Data:
Best Score: 0.685087
REMM: 0.685
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.099 (p=2.7E-1)

Phenotype Score: 0.502

Variant Score: 0.638

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 14-54879984-CAAAAA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.638 CONTRIBUTING VARIANT
Transcripts:
GCH1:ENST00000491895.7:c.344-14553_344-14549del:p.(=)
Pathogenicity Data:
Best Score: 0.637821
REMM: 0.638
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-54866377-A-G [0/1] rs1053950583
Variant score: 0.631
Transcripts:
GCH1:ENST00000491895.7:c.344-941T>C:p.(=)
Pathogenicity Data:
Best Score: 0.631369
REMM: 0.631
Frequency Data:
gnomAD_G_NFE: 0.0059%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 14-54879984-CA-C [0/1]
Variant score: 0.568
Transcripts:
GCH1:ENST00000491895.7:c.344-14549del:p.(=)
Pathogenicity Data:
Best Score: 0.568077
REMM: 0.568
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 14-54883398-AG-A [0/1]
Variant score: 0.413
Transcripts:
GCH1:ENST00000491895.7:c.344-17963del:p.(=)
Pathogenicity Data:
Best Score: 0.41274
REMM: 0.413
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 14-54880856-TATACTCC-T [0/1] rs201177497
Variant score: 0.284
Transcripts:
GCH1:ENST00000491895.7:c.344-15427_344-15421del:p.(=)
Pathogenicity Data:
Best Score: 0.323113
REMM: 0.323
Frequency Data:
gnomAD_G_AFR: 0.6401%
gnomAD_G_AMR: 0.0509%
gnomAD_G_NFE: 0.0193%
gnomAD_G_SAS: 0.1498%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 14-54880818-TATATATATACTCC-T [0/1] rs376868933
Variant score: 0.178
Transcripts:
GCH1:ENST00000491895.7:c.344-15395_344-15383del:p.(=)
Pathogenicity Data:
Best Score: 0.193587
REMM: 0.194
Frequency Data:
gnomAD_G_AFR: 0.4689%
gnomAD_G_AMR: 0.0654%
gnomAD_G_NFE: 0.0187%
gnomAD_G_SAS: 0.1151%
CODING_TRANSCRIPT_INTRON_VARIANT INS 14-54880805-T-TAC [0/1] rs1469279376
Variant score: 0.159
Transcripts:
GCH1:ENST00000491895.7:c.344-15370_344-15369insGT:p.(=)
Pathogenicity Data:
Best Score: 0.178885
REMM: 0.179
Frequency Data:
gnomAD_G_AFR: 0.6103%
gnomAD_G_AMR: 0.0757%
gnomAD_G_EAS: 0.0868%
gnomAD_G_NFE: 0.0381%
gnomAD_G_SAS: 0.0512%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-54871214-C-T [0/1] rs149096524
Variant score: 0.136
Transcripts:
GCH1:ENST00000491895.7:c.344-5778G>A:p.(=)
Pathogenicity Data:
Best Score: 0.199158
REMM: 0.199
Frequency Data:
UK10K: 0.0397%
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0261%
gnomAD_G_NFE: 0.0735%
gnomAD_G_SAS: 1.2023%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 14-54879420-CA-C [0/1]
Variant score: 0.134
Transcripts:
GCH1:ENST00000491895.7:c.344-13985del:p.(=)
Pathogenicity Data:
Best Score: 0.134299
REMM: 0.134
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 14-54880616-C-CAT [0/1] rs1319027866
Variant score: 0.132
Transcripts:
GCH1:ENST00000491895.7:c.344-15181_344-15180insAT:p.(=)
Pathogenicity Data:
Best Score: 0.132581
REMM: 0.133
Frequency Data:
gnomAD_G_AFR: 0.0460%
CODING_TRANSCRIPT_INTRON_VARIANT INS 14-54880569-C-CAT [0/1] rs369550067
Variant score: 0.123
Transcripts:
GCH1:ENST00000491895.7:c.344-15134_344-15133insAT:p.(=)
Pathogenicity Data:
Best Score: 0.131557
REMM: 0.132
Frequency Data:
gnomAD_G_AFR: 0.1052%
gnomAD_G_AMR: 0.3650%
gnomAD_G_NFE: 0.3923%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-54851580-C-T [0/1] rs373683877
Variant score: 0.105
Transcripts:
GCH1:ENST00000491895.7:c.510-4450G>A:p.(=)
Pathogenicity Data:
Best Score: 0.168014
REMM: 0.168
Frequency Data:
UK10K: 0.1851%
gnomAD_G_AFR: 0.0529%
gnomAD_G_AMR: 0.3725%
gnomAD_G_NFE: 0.2734%
gnomAD_G_SAS: 1.3278%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 14-54880518-CATAT-C [0/1] rs200255096
Variant score: 0.042
Transcripts:
GCH1:ENST00000491895.7:c.344-15086_344-15083del:p.(=)
Pathogenicity Data:
Best Score: 0.129578
REMM: 0.130
Frequency Data:
gnomAD_G_AFR: 1.7909%
gnomAD_G_AMR: 0.8614%
gnomAD_G_EAS: 0.1323%
gnomAD_G_NFE: 0.3575%
gnomAD_G_SAS: 0.8079%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 14-54880465-CAT-C [0/1] rs72187597
Variant score: 0.023
Transcripts:
GCH1:ENST00000491895.7:c.344-15031_344-15030del:p.(=)
Pathogenicity Data:
Best Score: 0.129116
REMM: 0.129
Frequency Data:
gnomAD_G_AFR: 1.9596%
gnomAD_G_AMR: 0.3261%
gnomAD_G_EAS: 0.9901%
gnomAD_G_NFE: 0.5257%
gnomAD_G_SAS: 1.4591%
THREE_PRIME_UTR_EXON_VARIANT SNV 14-54843650-C-T [0/1] rs886050548
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.000
Transcripts:
GCH1:ENST00000491895.7:c.*367G>A:p.(=)
Pathogenicity Data:
Best Score: 3.33333E-4
REMM: 0.000
Frequency Data:
gnomAD_E_AMR: 0.0092%
gnomAD_E_NFE: 0.0090%
gnomAD_E_SAS: 0.0026%
gnomAD_G_AMR: 0.0065%
gnomAD_G_NFE: 0.0103%

CDH2

Exomiser Score: 0.144 (p=2.3E-1)

Phenotype Score: 0.577

Variant Score: 0.600

Phenotype matches:
Phenotypic similarity 0.577 to Agenesis of corpus callosum, cardiac, ocular, and genital syndrome associated with CDH2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0002558, Supernumerary nipple
HP:0006625, Multifocal breast carcinoma - HP:0002558, Supernumerary nipple
Phenotypic similarity 0.276 to zebrafish mutant involving CDH2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0010131, cartilage element pectoral fin bud disorganized, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0010131, cartilage element pectoral fin bud disorganized, abnormal
Proximity score 0.505 in interactome to TWIST1 and phenotypic similarity 0.998 to Saethre-Chotzen syndrome with or without eyelid anomalies associated with TWIST1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.505 in interactome to TWIST1 and phenotypic similarity 0.356 to mouse mutant of TWIST1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000137, abnormal vertebrae morphology
HP:0006625, Multifocal breast carcinoma - MP:0000137, abnormal vertebrae morphology
Proximity score 0.505 in interactome to TWIST1 and phenotypic similarity 0.257 to fish mutant of TWIST1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0007632, notochord absent, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0007632, notochord absent, abnormal
Known diseases:
OMIM:618920 Arrhythmogenic right ventricular dysplasia 14 - autosomal dominant
OMIM:618929 Agenesis of corpus callosum, cardiac, ocular, and genital syndrome - autosomal dominant
OMIM:619957 ?Attention deficit-hyperactivity disorder 8 (unconfirmed)
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.144 (p=2.3E-1)

Phenotype Score: 0.577

Variant Score: 0.600

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.577 to OMIM:618929 Agenesis of corpus callosum, cardiac, ocular, and genital syndrome
Variants contributing to score:
MISSENSE_VARIANT SNV 18-28013892-T-G [0/1] rs202205175
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.600 CONTRIBUTING VARIANT
Transcripts:
CDH2:ENST00000269141.8:c.190A>C:p.(Asn64His)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_NFE: 0.0014%
gnomAD_G_NFE: 0.0029%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.132 (p=2.4E-1)

Phenotype Score: 0.505

Variant Score: 0.671

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 18-28077890-CA-C [1/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.671 CONTRIBUTING VARIANT
Transcripts:
CDH2:ENST00000269141.8:c.173-63982del:p.(=)
Pathogenicity Data:
Best Score: 0.670808
REMM: 0.671
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 18-28134135-CA-C [0/1]
Variant score: 0.480
Transcripts:
CDH2:ENST00000269141.8:c.172+13537del:p.(=)
Pathogenicity Data:
Best Score: 0.480085
REMM: 0.480
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 18-28134135-CAA-C [0/1]
Variant score: 0.480
Transcripts:
CDH2:ENST00000269141.8:c.172+13536_172+13537del:p.(=)
Pathogenicity Data:
Best Score: 0.480085
REMM: 0.480
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 18-28156532-C-A [0/1] rs4068901
Variant score: 0.297
Transcripts:
CDH2:ENST00000269141.8:c.61-8748G>T:p.(=)
Pathogenicity Data:
Best Score: 0.297404
REMM: 0.297
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 18-28156529-C-T [0/1]
Variant score: 0.293
Transcripts:
CDH2:ENST00000269141.8:c.61-8745G>A:p.(=)
Pathogenicity Data:
Best Score: 0.293103
REMM: 0.293
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 18-28156727-T-C [0/1] rs4068907
Variant score: 0.110
Transcripts:
CDH2:ENST00000269141.8:c.61-8943A>G:p.(=)
Pathogenicity Data:
Best Score: 0.329087
REMM: 0.329
Frequency Data:
gnomAD_G_AFR: 1.7775%
gnomAD_G_AMR: 1.6063%
gnomAD_G_EAS: 0.3205%
gnomAD_G_NFE: 1.4371%
gnomAD_G_SAS: 0.8838%
CODING_TRANSCRIPT_INTRON_VARIANT INS 18-28006563-C-CA [0/1] rs577869215
Variant score: 0.061
Transcripts:
CDH2:ENST00000269141.8:c.703-571_703-570insT:p.(=)
Pathogenicity Data:
Best Score: 0.1649
REMM: 0.165
Frequency Data:
gnomAD_G_AFR: 1.7362%
gnomAD_G_AMR: 0.2915%
gnomAD_G_EAS: 0.2951%
gnomAD_G_NFE: 0.2038%
gnomAD_G_SAS: 0.5806%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 18-28156683-C-T [0/1] rs139873247
Variant score: 0.057
Transcripts:
CDH2:ENST00000269141.8:c.61-8899G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0570302
REMM: 0.057
Frequency Data:
gnomAD_G_AFR: 0.0213%
gnomAD_G_EAS: 0.0498%
gnomAD_G_NFE: 0.0147%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 18-28144495-A-G [0/1]
Variant score: 0.045
Transcripts:
CDH2:ENST00000269141.8:c.172+3178T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0450861
REMM: 0.045
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 18-27995799-T-C [0/1]
Variant score: 0.001
Transcripts:
CDH2:ENST00000269141.8:c.1021-2162A>G:p.(=)
Pathogenicity Data:
Best Score: 6.66667E-4
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 18-28019405-C-T [0/1] rs576379794
Variant score: 0.000
Transcripts:
CDH2:ENST00000269141.8:c.173-5496G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_NFE: 0.0015%

SEMA3A

Exomiser Score: 0.140 (p=2.3E-1)

Phenotype Score: 0.620

Variant Score: 0.548

Phenotype matches:
Phenotypic similarity 0.620 to Kallmann syndrome associated with SEMA3A.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003187, Breast hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0003187, Breast hypoplasia
Phenotypic similarity 0.363 to mouse mutant involving SEMA3A.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000150, abnormal rib morphology
HP:0006625, Multifocal breast carcinoma - MP:0000150, abnormal rib morphology
Proximity score 0.508 in interactome to PLXND1 and phenotypic similarity 0.643 to Moebius syndrome associated with PLXND1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0100783, Breast aplasia
HP:0006625, Multifocal breast carcinoma - HP:0100783, Breast aplasia
Proximity score 0.508 in interactome to PLXND1 and phenotypic similarity 0.356 to mouse mutant of PLXND1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000141, abnormal vertebral body morphology
HP:0006625, Multifocal breast carcinoma - MP:0000141, abnormal vertebral body morphology
Known diseases:
OMIM:614897 Hypogonadotropic hypogonadism 16 with or without anosmia (susceptibility)
ORPHA:130 Brugada syndrome - autosomal dominant
ORPHA:478 Kallmann syndrome - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.140 (p=2.3E-1)

Phenotype Score: 0.620

Variant Score: 0.548

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.620 to ORPHA:478 Kallmann syndrome
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-84167056-T-TGC [0/1] rs71297133
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting, PP4]
Variant score: 0.548 CONTRIBUTING VARIANT
Transcripts:
SEMA3A:ENST00000265362.9:c.112+27418_112+27419insGC:p.(=)
Pathogenicity Data:
Best Score: 0.547863
REMM: 0.548
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.003 (p=6.0E-1)

Phenotype Score: 0.254

Variant Score: 0.529

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-84167056-T-TGC [0/1] rs71297133
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.548 CONTRIBUTING VARIANT
Transcripts:
SEMA3A:ENST00000265362.9:c.112+27418_112+27419insGC:p.(=)
Pathogenicity Data:
Best Score: 0.547863
REMM: 0.548
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84084042-G-C [0/1] rs148180251
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.510 CONTRIBUTING VARIANT
Transcripts:
SEMA3A:ENST00000265362.9:c.454-23484C>G:p.(=)
Pathogenicity Data:
Best Score: 0.745227
REMM: 0.745
Frequency Data:
UK10K: 0.4099%
gnomAD_G_AFR: 0.8361%
gnomAD_G_AMR: 0.3809%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.4916%
gnomAD_G_SAS: 1.2033%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84099061-T-C [1/1] rs79270863
Variant score: 0.493
Transcripts:
SEMA3A:ENST00000265362.9:c.453+11409A>G:p.(=)
Pathogenicity Data:
Best Score: 0.492798
REMM: 0.493
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-84020051-T-TC [0/1] rs542347973
Variant score: 0.473
Transcripts:
SEMA3A:ENST00000265362.9:c.668-5701_668-5700insG:p.(=)
Pathogenicity Data:
Best Score: 0.473454
REMM: 0.473
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84092183-T-A [0/1] rs11972825
Variant score: 0.460
Transcripts:
SEMA3A:ENST00000265362.9:c.453+18287A>T:p.(=)
Pathogenicity Data:
Best Score: 0.882662
REMM: 0.883
Frequency Data:
UK10K: 0.4099%
gnomAD_G_AFR: 1.5129%
gnomAD_G_AMR: 0.4970%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.5174%
gnomAD_G_SAS: 1.2417%
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-84136960-A-AGAAGGAAGGAAGGAAGGAAGGAAG [0/1] rs201748268
Variant score: 0.459
Transcripts:
SEMA3A:ENST00000265362.9:c.113-2010_113-2009insCTTCCTTCCTTCCTTCCTTCCTTC:p.(=)
Pathogenicity Data:
Best Score: 0.494826
REMM: 0.495
Frequency Data:
gnomAD_G_AFR: 0.4301%
gnomAD_G_AMR: 0.1083%
gnomAD_G_NFE: 0.0364%
gnomAD_G_SAS: 0.1162%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84061680-G-A [0/1] rs114354162
Variant score: 0.441
Transcripts:
SEMA3A:ENST00000265362.9:c.454-1122C>T:p.(=)
Pathogenicity Data:
Best Score: 0.945044
REMM: 0.945
Frequency Data:
UK10K: 0.3967%
gnomAD_G_AFR: 1.5980%
gnomAD_G_AMR: 0.4130%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.4884%
gnomAD_G_SAS: 1.5774%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-84020035-CTTTT-C [0/1]
Variant score: 0.401
Transcripts:
SEMA3A:ENST00000265362.9:c.668-5688_668-5685del:p.(=)
Pathogenicity Data:
Best Score: 0.400975
REMM: 0.401
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84128727-G-C [0/1] rs142841577
Variant score: 0.392
Transcripts:
SEMA3A:ENST00000265362.9:c.333+396C>G:p.(=)
Pathogenicity Data:
Best Score: 0.598615
REMM: 0.599
Frequency Data:
UK10K: 0.4232%
gnomAD_G_AFR: 0.7754%
gnomAD_G_AMR: 0.4256%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.5074%
gnomAD_G_SAS: 1.2671%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-84030987-GT-G [0/1]
Variant score: 0.386
Transcripts:
SEMA3A:ENST00000265362.9:c.667+15336del:p.(=)
Pathogenicity Data:
Best Score: 0.385946
REMM: 0.386
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84094935-T-C [0/1] rs138163786
Variant score: 0.363
Transcripts:
SEMA3A:ENST00000265362.9:c.453+15535A>G:p.(=)
Pathogenicity Data:
Best Score: 0.53652
REMM: 0.537
Frequency Data:
UK10K: 0.4099%
gnomAD_G_AFR: 0.8434%
gnomAD_G_AMR: 0.4077%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 0.5151%
gnomAD_G_SAS: 1.2225%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-84132660-GTGTTT-G [0/1] rs1218410631
Variant score: 0.344
Transcripts:
SEMA3A:ENST00000265362.9:c.270+2129_270+2133del:p.(=)
Pathogenicity Data:
Best Score: 0.343773
REMM: 0.344
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84119789-T-C [0/1] rs115325204
Variant score: 0.328
Transcripts:
SEMA3A:ENST00000265362.9:c.334-9200A>G:p.(=)
Pathogenicity Data:
Best Score: 0.577883
REMM: 0.578
Frequency Data:
UK10K: 0.4232%
gnomAD_G_AFR: 1.4340%
gnomAD_G_AMR: 0.5558%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.5104%
gnomAD_G_SAS: 1.2661%
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-84095279-A-ATATATATGGCATTATATGTATATAATGCATT [1/1] rs376433892
Variant score: 0.325
Transcripts:
SEMA3A:ENST00000265362.9:c.453+15190_453+15191insAATGCATTATATACATATAATGCCATATATA:p.(=)
Pathogenicity Data:
Best Score: 0.324671
REMM: 0.325
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84083328-T-C [0/1] rs112272193
Variant score: 0.323
Transcripts:
SEMA3A:ENST00000265362.9:c.454-22770A>G:p.(=)
Pathogenicity Data:
Best Score: 0.325453
REMM: 0.325
Frequency Data:
UK10K: 0.0529%
gnomAD_G_AFR: 0.0072%
gnomAD_G_AMR: 0.0327%
gnomAD_G_NFE: 0.0324%
gnomAD_G_SAS: 0.0414%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-84132662-GTTTTT-G [1/1] rs55830654
Variant score: 0.290
Transcripts:
SEMA3A:ENST00000265362.9:c.270+2127_270+2131del:p.(=)
Pathogenicity Data:
Best Score: 0.289983
REMM: 0.290
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84146646-A-T [0/1] rs141213957
Variant score: 0.286
Transcripts:
SEMA3A:ENST00000265362.9:c.113-11695T>A:p.(=)
Pathogenicity Data:
Best Score: 0.610619
REMM: 0.611
Frequency Data:
UK10K: 0.4232%
gnomAD_G_AFR: 0.7744%
gnomAD_G_AMR: 0.4576%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.5102%
gnomAD_G_SAS: 1.5942%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-84148974-TTAG-T [0/1] rs370970074
Variant score: 0.278
Transcripts:
SEMA3A:ENST00000265362.9:c.113-14026_113-14024del:p.(=)
Pathogenicity Data:
Best Score: 0.593473
REMM: 0.593
Frequency Data:
UK10K: 0.4232%
gnomAD_G_AFR: 0.6447%
gnomAD_G_AMR: 0.4379%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.5101%
gnomAD_G_SAS: 1.5955%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-84029478-TTAACTA-T [0/1] rs149780196
Variant score: 0.269
Transcripts:
SEMA3A:ENST00000265362.9:c.668-15133_668-15128del:p.(=)
Pathogenicity Data:
Best Score: 0.502845
REMM: 0.503
Frequency Data:
UK10K: 0.3967%
gnomAD_G_AFR: 0.7382%
gnomAD_G_AMR: 0.2943%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.4956%
gnomAD_G_SAS: 1.4901%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84069483-C-T [0/1] rs191149067
Variant score: 0.256
Transcripts:
SEMA3A:ENST00000265362.9:c.454-8925G>A:p.(=)
Pathogenicity Data:
Best Score: 0.504794
REMM: 0.505
Frequency Data:
UK10K: 0.4232%
gnomAD_G_AFR: 0.0675%
gnomAD_G_AMR: 0.2293%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.4723%
gnomAD_G_SAS: 1.5346%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84082586-T-G [0/1] rs11982684
Variant score: 0.251
Transcripts:
SEMA3A:ENST00000265362.9:c.454-22028A>C:p.(=)
Pathogenicity Data:
Best Score: 0.48286
REMM: 0.483
Frequency Data:
UK10K: 0.4099%
gnomAD_G_AFR: 1.5138%
gnomAD_G_AMR: 0.4709%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.4929%
gnomAD_G_SAS: 1.2428%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-83965650-ATATATATATATATATATT-A [0/1] rs1365862323
Variant score: 0.229
Transcripts:
SEMA3A:ENST00000265362.9:c.1718-2321_1718-2304del:p.(=)
Pathogenicity Data:
Best Score: 0.228576
REMM: 0.229
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84145451-T-G [0/1] rs145558351
Variant score: 0.223
Transcripts:
SEMA3A:ENST00000265362.9:c.113-10500A>C:p.(=)
Pathogenicity Data:
Best Score: 0.450924
REMM: 0.451
Frequency Data:
UK10K: 0.4232%
gnomAD_G_AFR: 0.7730%
gnomAD_G_AMR: 0.4647%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.5133%
gnomAD_G_SAS: 1.5547%
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-84062859-G-GC [0|1] rs759305153
Variant score: 0.190
Transcripts:
SEMA3A:ENST00000265362.9:c.454-2302_454-2301insG:p.(=)
Pathogenicity Data:
Best Score: 0.191442
REMM: 0.191
Frequency Data:
UK10K: 0.0661%
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-84062836-C-CG [0/1] rs1310212183
Variant score: 0.179
Transcripts:
SEMA3A:ENST00000265362.9:c.454-2279_454-2278insC:p.(=)
Pathogenicity Data:
Best Score: 0.178842
REMM: 0.179
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84079729-A-C [0|1] rs28880439
Variant score: 0.178
Transcripts:
SEMA3A:ENST00000265362.9:c.454-19171T>G:p.(=)
Pathogenicity Data:
Best Score: 0.178151
REMM: 0.178
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84150311-C-T [0/1] rs566743169
Variant score: 0.157
Transcripts:
SEMA3A:ENST00000265362.9:c.113-15360G>A:p.(=)
Pathogenicity Data:
Best Score: 0.183399
REMM: 0.183
Frequency Data:
gnomAD_G_AFR: 0.1924%
gnomAD_G_AMR: 0.3528%
gnomAD_G_NFE: 0.7247%
gnomAD_G_SAS: 0.4351%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84062525-G-C [0/1] rs141303483
Variant score: 0.155
Transcripts:
SEMA3A:ENST00000265362.9:c.454-1967C>G:p.(=)
Pathogenicity Data:
Best Score: 0.330466
REMM: 0.330
Frequency Data:
gnomAD_G_AFR: 1.5923%
gnomAD_G_AMR: 0.4117%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.4880%
gnomAD_G_SAS: 1.5748%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-84091130-AAG-A [0|1] rs1307171051
Variant score: 0.152
Transcripts:
SEMA3A:ENST00000265362.9:c.453+19338_453+19339del:p.(=)
Pathogenicity Data:
Best Score: 0.180989
REMM: 0.181
Frequency Data:
gnomAD_G_AFR: 0.7876%
gnomAD_G_AMR: 0.2813%
gnomAD_G_NFE: 0.4196%
gnomAD_G_SAS: 0.6000%
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-84080169-C-CA [0/1] rs531897376
Variant score: 0.143
Transcripts:
SEMA3A:ENST00000265362.9:c.454-19612_454-19611insT:p.(=)
Pathogenicity Data:
Best Score: 0.143347
REMM: 0.143
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84158879-A-T [0|1] rs117781758
Variant score: 0.134
Transcripts:
SEMA3A:ENST00000265362.9:c.113-23928T>A:p.(=)
Pathogenicity Data:
Best Score: 0.513245
REMM: 0.513
Frequency Data:
UK10K: 1.2034%
gnomAD_G_AFR: 1.3832%
gnomAD_G_AMR: 1.0800%
gnomAD_G_EAS: 0.0387%
gnomAD_G_NFE: 1.2445%
gnomAD_G_SAS: 1.8660%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84079777-T-C [0/1] rs146571640
Variant score: 0.109
Transcripts:
SEMA3A:ENST00000265362.9:c.454-19219A>G:p.(=)
Pathogenicity Data:
Best Score: 0.10895
REMM: 0.109
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84062863-A-G [0|1] rs1253587639
Variant score: 0.107
Transcripts:
SEMA3A:ENST00000265362.9:c.454-2305T>C:p.(=)
Pathogenicity Data:
Best Score: 0.140137
REMM: 0.140
Frequency Data:
gnomAD_G_AFR: 1.0175%
gnomAD_G_AMR: 0.5463%
gnomAD_G_EAS: 0.3155%
gnomAD_G_NFE: 0.4458%
gnomAD_G_SAS: 0.8653%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-84091141-AAGGAAGGAAG-A [1/1] rs1562774092
Variant score: 0.100
Transcripts:
SEMA3A:ENST00000265362.9:c.453+19319_453+19328del:p.(=)
Pathogenicity Data:
Best Score: 0.112306
REMM: 0.112
Frequency Data:
gnomAD_G_AFR: 0.5790%
gnomAD_G_AMR: 0.2019%
gnomAD_G_NFE: 0.2753%
gnomAD_G_SAS: 0.5348%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-84057751-GATAA-G [0/1] rs71297135
Variant score: 0.088
Transcripts:
SEMA3A:ENST00000265362.9:c.547+2710_547+2713del:p.(=)
Pathogenicity Data:
Best Score: 0.306373
REMM: 0.306
Frequency Data:
UK10K: 0.8199%
gnomAD_G_AFR: 1.1819%
gnomAD_G_AMR: 1.1833%
gnomAD_G_EAS: 0.8111%
gnomAD_G_NFE: 1.0899%
gnomAD_G_SAS: 1.8342%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-84091204-GAAAGAAAGA-G [0/1]
Variant score: 0.078
Transcripts:
SEMA3A:ENST00000265362.9:c.453+19257_453+19265del:p.(=)
Pathogenicity Data:
Best Score: 0.0784262
REMM: 0.078
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-83993016-A-G [0/1] rs1639599
Variant score: 0.075
Transcripts:
SEMA3A:ENST00000265362.9:c.1453-7539T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0749036
REMM: 0.075
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-83992965-A-AG [0/1] rs149986078
Variant score: 0.074
Transcripts:
SEMA3A:ENST00000265362.9:c.1453-7489_1453-7488insC:p.(=)
Pathogenicity Data:
Best Score: 0.0744083
REMM: 0.074
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-83980623-A-AAAAAAAAAAAAATATATAT [0/1] rs1310318006
Variant score: 0.071
Transcripts:
SEMA3A:ENST00000265362.9:c.1652+697_1652+698insATATATATTTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.071881
REMM: 0.072
Frequency Data:
gnomAD_G_AFR: 0.0166%
gnomAD_G_AMR: 0.0161%
gnomAD_G_NFE: 0.0531%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84063071-T-A [0/1] rs554619640
Variant score: 0.069
Transcripts:
SEMA3A:ENST00000265362.9:c.454-2513A>T:p.(=)
Pathogenicity Data:
Best Score: 0.130022
REMM: 0.130
Frequency Data:
gnomAD_G_AFR: 0.9551%
gnomAD_G_AMR: 0.3403%
gnomAD_G_EAS: 0.0196%
gnomAD_G_NFE: 0.4736%
gnomAD_G_SAS: 1.4910%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84137171-C-T [0/1] rs146183440
Variant score: 0.067
Transcripts:
SEMA3A:ENST00000265362.9:c.113-2220G>A:p.(=)
Pathogenicity Data:
Best Score: 0.127053
REMM: 0.127
Frequency Data:
UK10K: 0.4496%
gnomAD_G_AFR: 1.4993%
gnomAD_G_AMR: 0.5435%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 0.5120%
gnomAD_G_SAS: 1.2479%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-84091138-AGG-A [1|1] rs1393334691
Variant score: 0.065
Transcripts:
SEMA3A:ENST00000265362.9:c.453+19330_453+19331del:p.(=)
Pathogenicity Data:
Best Score: 0.109163
REMM: 0.109
Frequency Data:
gnomAD_G_AFR: 1.1744%
gnomAD_G_AMR: 0.3715%
gnomAD_G_NFE: 0.5504%
gnomAD_G_SAS: 1.3889%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84091155-G-A [0/1] rs376813445
Variant score: 0.053
Transcripts:
SEMA3A:ENST00000265362.9:c.453+19315C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0862901
REMM: 0.086
Frequency Data:
gnomAD_G_AFR: 1.3474%
gnomAD_G_AMR: 0.5224%
gnomAD_G_EAS: 0.1094%
gnomAD_G_NFE: 0.3593%
gnomAD_G_SAS: 0.6281%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84050350-C-G [0/1] rs182376428
Variant score: 0.044
Transcripts:
SEMA3A:ENST00000265362.9:c.548-3907G>C:p.(=)
Pathogenicity Data:
Best Score: 0.0872393
REMM: 0.087
Frequency Data:
gnomAD_G_AFR: 0.0698%
gnomAD_G_AMR: 0.2355%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.4910%
gnomAD_G_SAS: 1.5327%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84065257-C-T [0/1] rs866322661
Variant score: 0.043
Transcripts:
SEMA3A:ENST00000265362.9:c.454-4699G>A:p.(=)
Pathogenicity Data:
Best Score: 0.049494
REMM: 0.049
Frequency Data:
gnomAD_G_AFR: 0.4895%
gnomAD_G_AMR: 0.1259%
gnomAD_G_EAS: 0.1365%
gnomAD_G_NFE: 0.2594%
gnomAD_G_SAS: 0.6414%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84064641-T-G [0|1] rs576767020
Variant score: 0.029
Transcripts:
SEMA3A:ENST00000265362.9:c.454-4083A>C:p.(=)
Pathogenicity Data:
Best Score: 0.0287901
REMM: 0.029
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84064246-C-T [0/1] rs866839399
Variant score: 0.026
Transcripts:
SEMA3A:ENST00000265362.9:c.454-3688G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0540579
REMM: 0.054
Frequency Data:
gnomAD_G_AFR: 0.9428%
gnomAD_G_AMR: 0.3405%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 0.4825%
gnomAD_G_SAS: 1.5768%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84066430-G-T [0/1] rs1212911896
Variant score: 0.023
Transcripts:
SEMA3A:ENST00000265362.9:c.454-5872C>A:p.(=)
Pathogenicity Data:
Best Score: 0.0269317
REMM: 0.027
Frequency Data:
gnomAD_G_AFR: 0.7364%
gnomAD_G_AMR: 0.2430%
gnomAD_G_EAS: 0.0222%
gnomAD_G_NFE: 0.3971%
gnomAD_G_SAS: 0.7937%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84072465-G-T [0/1]
Variant score: 0.021
Transcripts:
SEMA3A:ENST00000265362.9:c.454-11907C>A:p.(=)
Pathogenicity Data:
Best Score: 0.0207913
REMM: 0.021
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84066367-G-A [0/1] rs567459561
Variant score: 0.020
Transcripts:
SEMA3A:ENST00000265362.9:c.454-5809C>T:p.(=)
Pathogenicity Data:
Best Score: 0.036579
REMM: 0.037
Frequency Data:
gnomAD_G_AFR: 0.9283%
gnomAD_G_AMR: 0.3228%
gnomAD_G_EAS: 0.0195%
gnomAD_G_NFE: 0.4698%
gnomAD_G_SAS: 1.4520%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84066921-C-T [0/1] rs546957839
Variant score: 0.019
Transcripts:
SEMA3A:ENST00000265362.9:c.454-6363G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0223532
REMM: 0.022
Frequency Data:
gnomAD_G_AFR: 0.1925%
gnomAD_G_AMR: 0.3528%
gnomAD_G_NFE: 0.7380%
gnomAD_G_SAS: 0.5191%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84056196-G-A [0/1] rs142249294
Variant score: 0.019
Transcripts:
SEMA3A:ENST00000265362.9:c.547+4269C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0367587
REMM: 0.037
Frequency Data:
UK10K: 0.3967%
gnomAD_G_AFR: 0.0723%
gnomAD_G_AMR: 0.2365%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.4966%
gnomAD_G_SAS: 1.5240%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84063851-T-C [0/1] rs866544770
Variant score: 0.018
Transcripts:
SEMA3A:ENST00000265362.9:c.454-3293A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0354266
REMM: 0.035
Frequency Data:
gnomAD_G_AFR: 0.9699%
gnomAD_G_AMR: 0.2915%
gnomAD_G_EAS: 0.0199%
gnomAD_G_NFE: 0.4740%
gnomAD_G_SAS: 1.5388%
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-83990805-C-CT [0/1] rs201186923
Variant score: 0.016
Transcripts:
SEMA3A:ENST00000265362.9:c.1453-5329_1453-5328insA:p.(=)
Pathogenicity Data:
Best Score: 0.0160754
REMM: 0.016
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84067545-G-T [0|1] rs530637328
Variant score: 0.016
Transcripts:
SEMA3A:ENST00000265362.9:c.454-6987C>A:p.(=)
Pathogenicity Data:
Best Score: 0.032396
REMM: 0.032
Frequency Data:
gnomAD_G_AFR: 0.9505%
gnomAD_G_AMR: 0.3473%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.4824%
gnomAD_G_SAS: 1.5625%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84067546-A-T [0|1] rs549170708
Variant score: 0.014
Transcripts:
SEMA3A:ENST00000265362.9:c.454-6988T>A:p.(=)
Pathogenicity Data:
Best Score: 0.027771
REMM: 0.028
Frequency Data:
gnomAD_G_AFR: 0.9510%
gnomAD_G_AMR: 0.3466%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.4822%
gnomAD_G_SAS: 1.5560%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84066920-G-A [0/1] rs375274228
Variant score: 0.014
Transcripts:
SEMA3A:ENST00000265362.9:c.454-6362C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0223528
REMM: 0.022
Frequency Data:
gnomAD_G_AFR: 0.8884%
gnomAD_G_AMR: 0.3083%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 0.4563%
gnomAD_G_SAS: 1.3536%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-83994228-G-T [0/1] rs199895095
Variant score: 0.013
Transcripts:
SEMA3A:ENST00000265362.9:c.1452+7727C>A:p.(=)
Pathogenicity Data:
Best Score: 0.0134341
REMM: 0.013
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-83993263-C-CTT [0/1] rs145216846
Variant score: 0.013
Transcripts:
SEMA3A:ENST00000265362.9:c.1453-7787_1453-7786insAA:p.(=)
Pathogenicity Data:
Best Score: 0.0130901
REMM: 0.013
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84062826-C-G [0|1] rs529252205
Variant score: 0.011
Transcripts:
SEMA3A:ENST00000265362.9:c.454-2268G>C:p.(=)
Pathogenicity Data:
Best Score: 0.0191774
REMM: 0.019
Frequency Data:
UK10K: 0.4099%
gnomAD_G_AFR: 1.4525%
gnomAD_G_AMR: 0.3766%
gnomAD_G_EAS: 0.0198%
gnomAD_G_NFE: 0.4217%
gnomAD_G_SAS: 0.9212%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84065655-A-C [0/1] rs865938377
Variant score: 0.010
Transcripts:
SEMA3A:ENST00000265362.9:c.454-5097T>G:p.(=)
Pathogenicity Data:
Best Score: 0.01565
REMM: 0.016
Frequency Data:
gnomAD_G_AFR: 0.8704%
gnomAD_G_AMR: 0.3274%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 0.4415%
gnomAD_G_SAS: 1.3158%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84051922-G-C [0/1] rs879570149
Variant score: 0.010
Transcripts:
SEMA3A:ENST00000265362.9:c.548-5479C>G:p.(=)
Pathogenicity Data:
Best Score: 0.011606
REMM: 0.012
Frequency Data:
gnomAD_G_AFR: 0.2045%
gnomAD_G_AMR: 0.3471%
gnomAD_G_EAS: 0.0198%
gnomAD_G_NFE: 0.8371%
gnomAD_G_SAS: 0.7582%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84063534-G-T [0/1] rs560105139
Variant score: 0.009
Transcripts:
SEMA3A:ENST00000265362.9:c.454-2976C>A:p.(=)
Pathogenicity Data:
Best Score: 0.0164667
REMM: 0.016
Frequency Data:
gnomAD_G_AFR: 0.8706%
gnomAD_G_AMR: 0.3107%
gnomAD_G_EAS: 0.0199%
gnomAD_G_NFE: 0.4569%
gnomAD_G_SAS: 1.4687%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84063477-C-T [0/1] rs529972433
Variant score: 0.009
Transcripts:
SEMA3A:ENST00000265362.9:c.454-2919G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0144655
REMM: 0.014
Frequency Data:
gnomAD_G_AFR: 0.8480%
gnomAD_G_AMR: 0.3097%
gnomAD_G_EAS: 0.0596%
gnomAD_G_NFE: 0.4462%
gnomAD_G_SAS: 1.3664%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84065757-C-G [0|1] rs866131346
Variant score: 0.008
Transcripts:
SEMA3A:ENST00000265362.9:c.454-5199G>C:p.(=)
Pathogenicity Data:
Best Score: 0.0138278
REMM: 0.014
Frequency Data:
gnomAD_G_AFR: 0.8957%
gnomAD_G_AMR: 0.3139%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.4544%
gnomAD_G_SAS: 1.3502%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84111702-G-A [0/1] rs116675873
Variant score: 0.006
Transcripts:
SEMA3A:ENST00000265362.9:c.334-1113C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0122012
REMM: 0.012
Frequency Data:
UK10K: 0.4232%
gnomAD_G_AFR: 1.4936%
gnomAD_G_AMR: 0.5558%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.5102%
gnomAD_G_SAS: 1.2640%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84063652-T-G [0/1] rs564589899
Variant score: 0.006
Transcripts:
SEMA3A:ENST00000265362.9:c.454-3094A>C:p.(=)
Pathogenicity Data:
Best Score: 0.0128238
REMM: 0.013
Frequency Data:
gnomAD_G_AFR: 0.9844%
gnomAD_G_AMR: 0.3477%
gnomAD_G_EAS: 0.0197%
gnomAD_G_NFE: 0.4832%
gnomAD_G_SAS: 1.5836%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84066786-C-G [0/1] rs574079519
Variant score: 0.006
Transcripts:
SEMA3A:ENST00000265362.9:c.454-6228G>C:p.(=)
Pathogenicity Data:
Best Score: 0.0103754
REMM: 0.010
Frequency Data:
gnomAD_G_AFR: 0.8772%
gnomAD_G_AMR: 0.8019%
gnomAD_G_EAS: 0.6602%
gnomAD_G_NFE: 0.4866%
gnomAD_G_SAS: 1.4429%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84068097-C-A [0/1] rs12707606
Variant score: 0.004
Transcripts:
SEMA3A:ENST00000265362.9:c.454-7539G>T:p.(=)
Pathogenicity Data:
Best Score: 0.00417262
REMM: 0.004
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84054808-T-C [1/1] rs4371954
Variant score: 0.004
Transcripts:
SEMA3A:ENST00000265362.9:c.547+5657A>G:p.(=)
Pathogenicity Data:
Best Score: 0.00395595
REMM: 0.004
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84080220-T-G [1/1]
Variant score: 0.003
Transcripts:
SEMA3A:ENST00000265362.9:c.454-19662A>C:p.(=)
Pathogenicity Data:
Best Score: 0.00338016
REMM: 0.003
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84144881-C-G [0/1] rs11982245
Variant score: 0.003
Transcripts:
SEMA3A:ENST00000265362.9:c.113-9930G>C:p.(=)
Pathogenicity Data:
Best Score: 0.00590357
REMM: 0.006
Frequency Data:
UK10K: 0.4232%
gnomAD_G_AFR: 0.7727%
gnomAD_G_AMR: 0.4580%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.5148%
gnomAD_G_SAS: 1.5742%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-83990360-G-T [0/1] rs60609947
Variant score: 0.003
Transcripts:
SEMA3A:ENST00000265362.9:c.1453-4883C>A:p.(=)
Pathogenicity Data:
Best Score: 0.00254762
REMM: 0.003
Frequency Data:
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0198%
gnomAD_G_EAS: 0.0196%
gnomAD_G_NFE: 0.0324%
gnomAD_G_SAS: 0.0627%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-83993684-T-C [0/1] rs28835109
Variant score: 0.002
Transcripts:
SEMA3A:ENST00000265362.9:c.1453-8207A>G:p.(=)
Pathogenicity Data:
Best Score: 0.00216071
REMM: 0.002
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-83993699-C-G [0/1] rs28856623
Variant score: 0.002
Transcripts:
SEMA3A:ENST00000265362.9:c.1453-8222G>C:p.(=)
Pathogenicity Data:
Best Score: 0.00216071
REMM: 0.002
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84067393-C-A [0/1] rs867159261
Variant score: 0.002
Transcripts:
SEMA3A:ENST00000265362.9:c.454-6835G>T:p.(=)
Pathogenicity Data:
Best Score: 0.00347183
REMM: 0.003
Frequency Data:
gnomAD_G_AFR: 0.9361%
gnomAD_G_AMR: 0.3536%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.4723%
gnomAD_G_SAS: 1.4369%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84053156-A-G [0/1] rs200216881
Variant score: 0.001
Transcripts:
SEMA3A:ENST00000265362.9:c.548-6713T>C:p.(=)
Pathogenicity Data:
Best Score: 0.001
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-83966704-G-A [0/1] rs1253929621
Variant score: 0.001
Transcripts:
SEMA3A:ENST00000265362.9:c.1718-3357C>T:p.(=)
Pathogenicity Data:
Best Score: 0.001
REMM: 0.001
Frequency Data:
gnomAD_G_AFR: 0.0077%
gnomAD_G_NFE: 0.0034%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-83990455-G-A [0/1] rs1088371
Variant score: 0.001
Transcripts:
SEMA3A:ENST00000265362.9:c.1453-4978C>T:p.(=)
Pathogenicity Data:
Best Score: 7.5E-4
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84066122-G-A [0|1] rs567719435
Variant score: 0.001
Transcripts:
SEMA3A:ENST00000265362.9:c.454-5564C>T:p.(=)
Pathogenicity Data:
Best Score: 7.5E-4
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-84158148-C-CT [1/1] rs1187182577
Variant score: 0.001
Transcripts:
SEMA3A:ENST00000265362.9:c.113-23198_113-23197insA:p.(=)
Pathogenicity Data:
Best Score: 6.66667E-4
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84047855-G-A [0/1]
Variant score: 0.001
Transcripts:
SEMA3A:ENST00000265362.9:c.548-1412C>T:p.(=)
Pathogenicity Data:
Best Score: 5.0E-4
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84064829-C-T [0/1] rs1379553844
Variant score: 0.000
Transcripts:
SEMA3A:ENST00000265362.9:c.454-4271G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00158095
REMM: 0.002
Frequency Data:
gnomAD_G_AFR: 1.9802%
gnomAD_G_AMR: 0.3826%
gnomAD_G_NFE: 0.2899%
gnomAD_G_SAS: 0.4898%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84009682-A-G [0/1] rs139492661
Variant score: 0.000
Transcripts:
SEMA3A:ENST00000265362.9:c.995+1340T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.8992%
gnomAD_G_AFR: 0.2117%
gnomAD_G_AMR: 0.3536%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.8660%
gnomAD_G_SAS: 0.8088%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84030878-G-A [0/1] rs182345978
Variant score: 0.000
Transcripts:
SEMA3A:ENST00000265362.9:c.667+15446C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.8860%
gnomAD_G_AFR: 0.2141%
gnomAD_G_AMR: 0.3634%
gnomAD_G_EAS: 0.0198%
gnomAD_G_NFE: 0.8716%
gnomAD_G_SAS: 0.7997%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84065556-A-T [0/1] rs1272096424
Variant score: 0.000
Transcripts:
SEMA3A:ENST00000265362.9:c.454-4998T>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84068576-C-T [0/1] rs149401528
Variant score: 0.000
Transcripts:
SEMA3A:ENST00000265362.9:c.454-8018G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.3967%
gnomAD_G_AFR: 0.9500%
gnomAD_G_AMR: 0.3474%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.4885%
gnomAD_G_SAS: 1.5385%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-84086482-TTATATTTACATATAATATATTATTATATTATATTTATATATAATATATTATTA-T [1|1] nsv6266863
Variant score: 0.000
Transcripts:
SEMA3A:ENST00000265362.9:c.453+23935_453+23987del:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84147986-T-G [0/1] rs149970871
Variant score: 0.000
Transcripts:
SEMA3A:ENST00000265362.9:c.113-13035A>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.3967%
gnomAD_G_AFR: 0.7654%
gnomAD_G_AMR: 0.4644%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.5072%
gnomAD_G_SAS: 1.5975%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-84149183-G-T [0/1] rs761215671
Variant score: 0.000
Transcripts:
SEMA3A:ENST00000265362.9:c.113-14232C>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.0397%
gnomAD_G_AFR: 0.0096%
gnomAD_G_AMR: 0.0196%
gnomAD_G_NFE: 0.0250%
gnomAD_G_SAS: 0.0621%

CNOT2

Exomiser Score: 0.139 (p=2.3E-1)

Phenotype Score: 0.501

Variant Score: 0.681

Phenotype matches:
Proximity score 0.501 in interactome to EIF4A2 and phenotypic similarity 0.643 to Neurodevelopmental disorder with hypotonia and speech delay, with or without seizures associated with EIF4A2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Known diseases:
OMIM:618608 Intellectual developmental disorder with nasal speech, dysmorphic facies, and variable skeletal anomalies - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.139 (p=2.3E-1)

Phenotype Score: 0.501

Variant Score: 0.681

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-70283930-A-ATTT [0/1] rs776119049
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.681 CONTRIBUTING VARIANT
Transcripts:
CNOT2:ENST00000229195.8:c.48+5656_48+5657insTTT:p.(=)
Pathogenicity Data:
Best Score: 0.681362
REMM: 0.681
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.009 (p=4.8E-1)

Phenotype Score: 0.251

Variant Score: 0.650

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-70283930-A-ATTT [0/1] rs776119049
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.681 CONTRIBUTING VARIANT
Transcripts:
CNOT2:ENST00000229195.8:c.48+5656_48+5657insTTT:p.(=)
Pathogenicity Data:
Best Score: 0.681362
REMM: 0.681
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-70281816-T-TTAAATTTAAACTCATTTAAATTAAATAAATTTAAACTCATTTAAATTAAATAAATTTAAACTCATTTAAATTAAA [0/1] rs71098085
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.618 CONTRIBUTING VARIANT
Transcripts:
CNOT2:ENST00000229195.8:c.48+3542_48+3543insTAAATTTAAACTCATTTAAATTAAATAAATTTAAACTCATTTAAATTAAATAAATTTAAACTCATTTAAATTAAA:p.(=)
Pathogenicity Data:
Best Score: 0.628181
REMM: 0.628
Frequency Data:
gnomAD_G_AFR: 0.1125%
gnomAD_G_NFE: 0.0443%
Other passed variants:
INTERGENIC_VARIANT DEL 12-70227001-CAA-C [0/1]
Variant score: 0.351
Transcripts:
CNOT2:ENST00000229195.8::
Pathogenicity Data:
Best Score: 0.350748
REMM: 0.351
Frequency Data:
No frequency data
THREE_PRIME_UTR_EXON_VARIANT INS 12-70353913-T-TAAA [0/1] rs35192504
Variant score: 0.236
Transcripts:
CNOT2:ENST00000229195.8:c.*21_*23dup:p.(=)
Pathogenicity Data:
Best Score: 0.985514
REMM: 0.986
Frequency Data:
gnomAD_E_AFR: 0.7472%
gnomAD_E_AMR: 1.8895%
gnomAD_E_EAS: 1.0449%
gnomAD_E_NFE: 0.5776%
gnomAD_E_SAS: 1.2971%
gnomAD_G_AFR: 0.6688%
gnomAD_G_AMR: 0.8525%
gnomAD_G_EAS: 0.7149%
gnomAD_G_NFE: 0.7400%
gnomAD_G_SAS: 1.3939%
FIVE_PRIME_UTR_INTRON_VARIANT DEL 12-70261305-CT-C [0/1] rs71437141
Variant score: 0.198
Transcripts:
CNOT2:ENST00000229195.8:c.-95-16826del:p.(=)
Pathogenicity Data:
Best Score: 0.197727
REMM: 0.198
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT DEL 12-70256582-TA-T [0/1] rs372870920
Variant score: 0.027
Transcripts:
CNOT2:ENST00000229195.8:c.-96+13103del:p.(=)
Pathogenicity Data:
Best Score: 0.0288702
REMM: 0.029
Frequency Data:
gnomAD_G_AFR: 0.1559%
gnomAD_G_AMR: 0.0583%
gnomAD_G_EAS: 0.3900%
gnomAD_G_NFE: 0.1131%
gnomAD_G_SAS: 0.0638%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-70295894-C-T [0/1] rs534016127
Variant score: 0.002
Transcripts:
CNOT2:ENST00000229195.8:c.49-15001C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00195357
REMM: 0.002
Frequency Data:
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0197%
gnomAD_G_NFE: 0.0603%
gnomAD_G_SAS: 0.0207%

VIPR1

Exomiser Score: 0.136 (p=2.4E-1)

Phenotype Score: 0.502

Variant Score: 0.677

Phenotype matches:
Proximity score 0.502 in interactome to FSHR and phenotypic similarity 0.676 to 46,XX gonadal dysgenesis associated with FSHR.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
HP:0006625, Multifocal breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
Proximity score 0.502 in interactome to FSHR and phenotypic similarity 0.368 to mouse mutant of FSHR.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000160, kyphosis
HP:0006625, Multifocal breast carcinoma - MP:0000160, kyphosis
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.136 (p=2.4E-1)

Phenotype Score: 0.502

Variant Score: 0.677

No phenotype matches to diseases with this MOI.
Variants contributing to score:
INTERGENIC_VARIANT SNV 3-42496698-T-C [0/1] rs1472305262
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.677 CONTRIBUTING VARIANT
Transcripts:
VIPR1:ENST00000325123.5::
Pathogenicity Data:
Best Score: 0.677574
REMM: 0.678
Frequency Data:
gnomAD_G_NFE: 0.0015%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.099 (p=2.6E-1)

Phenotype Score: 0.502

Variant Score: 0.638

No phenotype matches to diseases with this MOI.
Variants contributing to score:
INTERGENIC_VARIANT SNV 3-42496698-T-C [0/1] rs1472305262
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.677 CONTRIBUTING VARIANT
Transcripts:
VIPR1:ENST00000325123.5::
Pathogenicity Data:
Best Score: 0.677574
REMM: 0.678
Frequency Data:
gnomAD_G_NFE: 0.0015%
MISSENSE_VARIANT SNV 3-42531489-C-G [0/1] rs755471706
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.599 CONTRIBUTING VARIANT
Transcripts:
VIPR1:ENST00000325123.5:c.809C>G:p.(Thr270Ser)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AMR: 0.0048%
gnomAD_E_NFE: 0.0060%
gnomAD_E_SAS: 0.0024%
gnomAD_G_NFE: 0.0073%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT INS 3-42522102-T-TATATATA [1|1]
Variant score: 0.163
Transcripts:
VIPR1:ENST00000325123.5:c.292+2772_292+2773insATATATA:p.(=)
Pathogenicity Data:
Best Score: 0.163225
REMM: 0.163
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-42522104-T-A [1|1] rs1376344622
Variant score: 0.079
Transcripts:
VIPR1:ENST00000325123.5:c.292+2774T>A:p.(=)
Pathogenicity Data:
Best Score: 0.0792206
REMM: 0.079
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 3-42504763-T-TG [0|1]
Variant score: 0.006
Transcripts:
VIPR1:ENST00000325123.5:c.78+1950_78+1951insG:p.(=)
Pathogenicity Data:
Best Score: 0.00551548
REMM: 0.006
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-42504772-G-A [0|1] rs56184136
Variant score: 0.003
Transcripts:
VIPR1:ENST00000325123.5:c.78+1959G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0032
REMM: 0.003
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-42532225-G-C [0/1] rs200754044
Variant score: 0.002
Transcripts:
VIPR1:ENST00000325123.5:c.919-17G>C:p.(=)
Pathogenicity Data:
Best Score: 0.00166667
REMM: 0.002
Frequency Data:
UK10K: 0.1190%
gnomAD_E_AFR: 0.0149%
gnomAD_E_AMR: 0.0604%
gnomAD_E_NFE: 0.1321%
gnomAD_E_SAS: 0.0313%
gnomAD_G_AFR: 0.0096%
gnomAD_G_AMR: 0.0654%
gnomAD_G_NFE: 0.1485%
gnomAD_G_SAS: 0.0208%

DRD5

Exomiser Score: 0.128 (p=2.4E-1)

Phenotype Score: 0.502

Variant Score: 0.670

Phenotype matches:
Proximity score 0.502 in interactome to FSHR and phenotypic similarity 0.676 to 46,XX gonadal dysgenesis associated with FSHR.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
HP:0006625, Multifocal breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
Proximity score 0.502 in interactome to FSHR and phenotypic similarity 0.368 to mouse mutant of FSHR.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000160, kyphosis
HP:0006625, Multifocal breast carcinoma - MP:0000160, kyphosis
Known diseases:
OMIM:143465 Attention deficit-hyperactivity disorder, susceptibility to (susceptibility)
OMIM:606798 Blepharospasm, primary benign (susceptibility)
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.128 (p=2.4E-1)

Phenotype Score: 0.502

Variant Score: 0.670

No phenotype matches to diseases with this MOI.
Variants contributing to score:
INTERGENIC_VARIANT SNV 4-9773739-G-A [0/1] rs371121972
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.670 CONTRIBUTING VARIANT
Transcripts:
DRD5:ENST00000304374.4::
Pathogenicity Data:
Best Score: 0.673403
REMM: 0.673
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AFR: 0.0072%
gnomAD_G_AMR: 0.0065%
gnomAD_G_EAS: 0.0387%
gnomAD_G_NFE: 0.0074%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.008 (p=5.0E-1)

Phenotype Score: 0.251

Variant Score: 0.633

No phenotype matches to diseases with this MOI.
Variants contributing to score:
INTERGENIC_VARIANT SNV 4-9773739-G-A [0/1] rs371121972
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.670 CONTRIBUTING VARIANT
Transcripts:
DRD5:ENST00000304374.4::
Pathogenicity Data:
Best Score: 0.673403
REMM: 0.673
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AFR: 0.0072%
gnomAD_G_AMR: 0.0065%
gnomAD_G_EAS: 0.0387%
gnomAD_G_NFE: 0.0074%
MISSENSE_VARIANT SNV 4-9782345-T-C [0/1] rs147655139
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.596 CONTRIBUTING VARIANT
Transcripts:
DRD5:ENST00000304374.4:c.316T>C:p.(Tyr106His)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 0.0090%
gnomAD_E_AMR: 0.0134%
gnomAD_E_NFE: 0.0492%
gnomAD_E_SAS: 0.0035%
gnomAD_G_AFR: 0.0072%
gnomAD_G_NFE: 0.0529%
Other passed variants:
UPSTREAM_GENE_VARIANT DEL 4-9778049-TTTCTTTCCTTCCTTCCTTCC-T [0/1] rs1180354755
Variant score: 0.474
Transcripts:
DRD5:ENST00000304374.4::
Pathogenicity Data:
Best Score: 0.473973
REMM: 0.474
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT DEL 4-9778045-TTTCTTTCTTTCC-T [0/1] rs1233217314
Variant score: 0.227
Transcripts:
DRD5:ENST00000304374.4::
Pathogenicity Data:
Best Score: 0.28047
REMM: 0.280
Frequency Data:
gnomAD_G_AFR: 0.1219%
gnomAD_G_AMR: 0.3577%
gnomAD_G_NFE: 0.8770%
UPSTREAM_GENE_VARIANT SNV 4-9778309-G-A [0/1] rs142750391
Variant score: 0.013
Transcripts:
DRD5:ENST00000304374.4::
Pathogenicity Data:
Best Score: 0.0222694
REMM: 0.022
Frequency Data:
UK10K: 1.3092%
gnomAD_G_AFR: 0.2147%
gnomAD_G_AMR: 0.7473%
gnomAD_G_NFE: 1.4104%
gnomAD_G_SAS: 0.4359%

HSPG2

Exomiser Score: 0.126 (p=2.4E-1)

Phenotype Score: 0.548

Variant Score: 0.616

Phenotype matches:
Phenotypic similarity 0.548 to Dyssegmental dysplasia, Silverman-Handmaker type associated with HSPG2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0005257, Thoracic hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0005257, Thoracic hypoplasia
Phenotypic similarity 0.459 to mouse mutant involving HSPG2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0004134, abnormal chest morphology
HP:0006625, Multifocal breast carcinoma - MP:0004134, abnormal chest morphology
Proximity score 0.508 in interactome to HS6ST1 and phenotypic similarity 0.620 to Kallmann syndrome associated with HS6ST1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003187, Breast hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0003187, Breast hypoplasia
Proximity score 0.508 in interactome to HS6ST1 and phenotypic similarity 0.318 to mouse mutant of HS6ST1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002113, abnormal skeleton development
HP:0006625, Multifocal breast carcinoma - MP:0002113, abnormal skeleton development
Known diseases:
OMIM:224410 Dyssegmental dysplasia, Silverman-Handmaker type - autosomal recessive
OMIM:255800 Schwartz-Jampel syndrome, type 1 - autosomal recessive
ORPHA:1606 1p36 deletion syndrome (CNV)
ORPHA:1865 Dyssegmental dysplasia, Silverman-Handmaker type - autosomal recessive
ORPHA:800 Schwartz-Jampel syndrome - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.126 (p=2.4E-1)

Phenotype Score: 0.548

Variant Score: 0.616

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.548 to OMIM:224410 Dyssegmental dysplasia, Silverman-Handmaker type
Phenotypic similarity 0.508 to ORPHA:1865 Dyssegmental dysplasia, Silverman-Handmaker type
Phenotypic similarity 0.453 to ORPHA:800 Schwartz-Jampel syndrome
Phenotypic similarity 0.451 to OMIM:255800 Schwartz-Jampel syndrome, type 1
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-21926761-CA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.620 CONTRIBUTING VARIANT
Transcripts:
HSPG2:ENST00000374695.8:c.63+10393del:p.(=)
Pathogenicity Data:
Best Score: 0.619855
REMM: 0.620
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-21867614-G-A [0/1] rs71636994
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.612 CONTRIBUTING VARIANT
Transcripts:
HSPG2:ENST00000374695.8:c.4222-1805C>T:p.(=)
Pathogenicity Data:
Best Score: 0.701967
REMM: 0.702
Frequency Data:
UK10K: 0.6083%
gnomAD_G_AFR: 0.0891%
gnomAD_G_AMR: 0.3272%
gnomAD_G_NFE: 0.6646%
gnomAD_G_SAS: 0.1657%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.007 (p=5.1E-1)

Phenotype Score: 0.254

Variant Score: 0.620

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-21926761-CA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.620 CONTRIBUTING VARIANT
Transcripts:
HSPG2:ENST00000374695.8:c.63+10393del:p.(=)
Pathogenicity Data:
Best Score: 0.619855
REMM: 0.620
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-21863060-C-CAAAAAAAAAAAAAAAA [0/1]
Variant score: 0.159
Transcripts:
HSPG2:ENST00000374695.8:c.4741-946_4741-945insTTTTTTTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.159107
REMM: 0.159
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-21863060-CA-C [0/1]
Variant score: 0.159
Transcripts:
HSPG2:ENST00000374695.8:c.4741-946del:p.(=)
Pathogenicity Data:
Best Score: 0.159107
REMM: 0.159
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-21932666-G-C [0/1] rs577002584
Variant score: 0.152
Transcripts:
HSPG2:ENST00000374695.8:c.63+4489C>G:p.(=)
Pathogenicity Data:
Best Score: 0.15283
REMM: 0.153
Frequency Data:
UK10K: 0.0397%
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0065%
gnomAD_G_NFE: 0.0617%
SYNONYMOUS_VARIANT SNV 1-21874411-G-A [0/1] rs371519713
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:1, LB:1)
Variant score: 0.099
Transcripts:
HSPG2:ENST00000374695.8:c.3651C>T:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 0.0060%
gnomAD_E_NFE: 0.0071%
gnomAD_E_SAS: 0.0523%
gnomAD_G_AFR: 0.0072%
gnomAD_G_AMR: 0.0196%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.0088%
gnomAD_G_SAS: 0.0829%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-21866209-G-A [0/1]
Variant score: 0.099
Transcripts:
HSPG2:ENST00000374695.8:c.4222-400C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0988075
REMM: 0.099
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-21921554-G-T [0/1] rs35542927
Variant score: 0.068
Transcripts:
HSPG2:ENST00000374695.8:c.63+15601C>A:p.(=)
Pathogenicity Data:
Best Score: 0.463119
REMM: 0.463
Frequency Data:
UK10K: 0.7273%
gnomAD_G_AFR: 0.1323%
gnomAD_G_AMR: 0.3924%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.7852%
gnomAD_G_SAS: 1.9876%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-21837405-C-T [0/1] rs34602840
Variant score: 0.000
Transcripts:
HSPG2:ENST00000374695.8:c.10151-399G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.6348%
gnomAD_G_AFR: 0.1012%
gnomAD_G_AMR: 0.3928%
gnomAD_G_NFE: 0.6926%
gnomAD_G_SAS: 1.7435%

ENPP1

Exomiser Score: 0.126 (p=2.4E-1)

Phenotype Score: 0.501

Variant Score: 0.669

Phenotype matches:
Phenotypic similarity 0.504 to Pseudoxanthoma elasticum associated with ENPP1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000765, Abnormal thorax morphology
HP:0006625, Multifocal breast carcinoma - HP:0000765, Abnormal thorax morphology
Phenotypic similarity 0.372 to mouse mutant involving ENPP1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0010099, abnormal thoracic cage shape
HP:0006625, Multifocal breast carcinoma - MP:0010099, abnormal thoracic cage shape
Phenotypic similarity 0.500 to zebrafish mutant involving ENPP1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0006783, axial fin skeleton mineralized, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0006783, axial fin skeleton mineralized, abnormal
Proximity score 0.501 in interactome to INSR and phenotypic similarity 0.620 to Leprechaunism associated with INSR.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0004405, Prominent nipples
HP:0006625, Multifocal breast carcinoma - HP:0004405, Prominent nipples
Proximity score 0.501 in interactome to INSR and phenotypic similarity 0.273 to fish mutant of INSR.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0103759, scale fin decreased size, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0103759, scale fin decreased size, abnormal
Known diseases:
OMIM:125853 Diabetes mellitus, non-insulin-dependent, susceptibility to (susceptibility)
OMIM:208000 Arterial calcification, generalized, of infancy, 1 - autosomal recessive
OMIM:601665 Obesity, susceptibility to (susceptibility)
OMIM:613312 Hypophosphatemic rickets, autosomal recessive, 2 - autosomal recessive
OMIM:615522 Cole disease - autosomal dominant
ORPHA:289176 Autosomal recessive hypophosphatemic rickets - autosomal recessive
ORPHA:51608 Generalized arterial calcification of infancy - autosomal recessive
ORPHA:758 Pseudoxanthoma elasticum - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.126 (p=2.4E-1)

Phenotype Score: 0.501

Variant Score: 0.669

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-131845043-GTT-G [0/1] rs142380855
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.669 CONTRIBUTING VARIANT
Transcripts:
ENPP1:ENST00000647893.1:c.241-2732_241-2731del:p.(=)
Pathogenicity Data:
Best Score: 0.668915
REMM: 0.669
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.114 (p=2.5E-1)

Phenotype Score: 0.504

Variant Score: 0.653

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.504 to ORPHA:758 Pseudoxanthoma elasticum
Phenotypic similarity 0.471 to ORPHA:51608 Generalized arterial calcification of infancy
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-131845043-GTT-G [0/1] rs142380855
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.669 CONTRIBUTING VARIANT
Transcripts:
ENPP1:ENST00000647893.1:c.241-2732_241-2731del:p.(=)
Pathogenicity Data:
Best Score: 0.668915
REMM: 0.669
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-131845043-GT-G [0/1] rs142380855
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.637 CONTRIBUTING VARIANT
Transcripts:
ENPP1:ENST00000647893.1:c.241-2732del:p.(=)
Pathogenicity Data:
Best Score: 0.636734
REMM: 0.637
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-131877866-A-AAAAAAAAT [0/1]
Variant score: 0.355
Transcripts:
ENPP1:ENST00000647893.1:c.1894-676_1894-675insAAAAAAAT:p.(=)
Pathogenicity Data:
Best Score: 0.35499
REMM: 0.355
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 6-131901937-GA-G [0/1]
Variant score: 0.338
Transcripts:
ENPP1:ENST00000647893.1::
Pathogenicity Data:
Best Score: 0.338233
REMM: 0.338
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 6-131901940-A-T [0|1]
Variant score: 0.324
Transcripts:
ENPP1:ENST00000647893.1::
Pathogenicity Data:
Best Score: 0.323759
REMM: 0.324
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 6-131901944-AC-A [0|1]
Variant score: 0.321
Transcripts:
ENPP1:ENST00000647893.1::
Pathogenicity Data:
Best Score: 0.32077
REMM: 0.321
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 6-131901923-A-G [0|1]
Variant score: 0.290
Transcripts:
ENPP1:ENST00000647893.1::
Pathogenicity Data:
Best Score: 0.290438
REMM: 0.290
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 6-131901953-C-T [0|1] rs183799683
Variant score: 0.290
Transcripts:
ENPP1:ENST00000647893.1::
Pathogenicity Data:
Best Score: 0.2919
REMM: 0.292
Frequency Data:
gnomAD_G_AFR: 0.0151%
gnomAD_G_AMR: 0.0199%
gnomAD_G_EAS: 0.0541%
gnomAD_G_NFE: 0.0114%
gnomAD_G_SAS: 0.0394%
INTERGENIC_VARIANT SNV 6-131901922-C-T [0|1] rs6904066
Variant score: 0.289
Transcripts:
ENPP1:ENST00000647893.1::
Pathogenicity Data:
Best Score: 0.289438
REMM: 0.289
Frequency Data:
No frequency data
THREE_PRIME_UTR_EXON_VARIANT DEL 6-131893949-CTTTT-C [0/1] rs564304453
Variant score: 0.229
Transcripts:
ENPP1:ENST00000647893.1:c.*3465_*3468del:p.(=)
Pathogenicity Data:
Best Score: 0.22929
REMM: 0.229
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 6-131903370-A-G [0|1] rs538569429
Variant score: 0.153
Transcripts:
ENPP1:ENST00000647893.1::
Pathogenicity Data:
Best Score: 0.153377
REMM: 0.153
Frequency Data:
No frequency data
INTERGENIC_VARIANT INS 6-131906359-G-GC [0/1] rs202212408
Variant score: 0.122
Transcripts:
ENPP1:ENST00000647893.1::
Pathogenicity Data:
Best Score: 0.122414
REMM: 0.122
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 6-131903374-T-G [0|1] rs578080007
Variant score: 0.118
Transcripts:
ENPP1:ENST00000647893.1::
Pathogenicity Data:
Best Score: 0.13179
REMM: 0.132
Frequency Data:
gnomAD_G_AFR: 0.3150%
gnomAD_G_AMR: 0.5702%
gnomAD_G_EAS: 0.1550%
gnomAD_G_NFE: 0.1363%
gnomAD_G_SAS: 0.0444%
INTERGENIC_VARIANT SNV 6-131904826-G-C [0/1] rs9375839
Variant score: 0.114
Transcripts:
ENPP1:ENST00000647893.1::
Pathogenicity Data:
Best Score: 0.113938
REMM: 0.114
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 6-131904860-T-C [0|1] rs9388931
Variant score: 0.100
Transcripts:
ENPP1:ENST00000647893.1::
Pathogenicity Data:
Best Score: 0.0998313
REMM: 0.100
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 6-131904861-A-G [0|1] rs9388932
Variant score: 0.099
Transcripts:
ENPP1:ENST00000647893.1::
Pathogenicity Data:
Best Score: 0.0985397
REMM: 0.099
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 6-131800396-CT-C [0/1] rs61305574
Variant score: 0.098
Transcripts:
ENPP1:ENST00000647893.1::
Pathogenicity Data:
Best Score: 0.0975825
REMM: 0.098
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 6-131904917-T-G [0|1] rs372459002
Variant score: 0.072
Transcripts:
ENPP1:ENST00000647893.1::
Pathogenicity Data:
Best Score: 0.0722278
REMM: 0.072
Frequency Data:
gnomAD_G_AFR: 0.0059%
gnomAD_G_NFE: 0.0064%
INTERGENIC_VARIANT DEL 6-131901955-GCT-G [0|1] rs374022465
Variant score: 0.058
Transcripts:
ENPP1:ENST00000647893.1::
Pathogenicity Data:
Best Score: 0.0578159
REMM: 0.058
Frequency Data:
No frequency data
THREE_PRIME_UTR_EXON_VARIANT DEL 6-131893949-CT-C [0/1] rs564304453
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.057
Transcripts:
ENPP1:ENST00000647893.1:c.*3468del:p.(=)
Pathogenicity Data:
Best Score: 0.0565536
REMM: 0.057
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 6-131904889-T-C [0/1] rs147492723
Variant score: 0.046
Transcripts:
ENPP1:ENST00000647893.1::
Pathogenicity Data:
Best Score: 0.0591806
REMM: 0.059
Frequency Data:
gnomAD_G_AFR: 0.9665%
gnomAD_G_AMR: 0.0720%
gnomAD_G_EAS: 0.0896%
gnomAD_G_NFE: 0.0645%
gnomAD_G_SAS: 0.1806%
INTERGENIC_VARIANT SNV 6-131904920-C-T [0|1] rs149626813
Variant score: 0.020
Transcripts:
ENPP1:ENST00000647893.1::
Pathogenicity Data:
Best Score: 0.0575139
REMM: 0.058
Frequency Data:
gnomAD_G_AFR: 1.7711%
gnomAD_G_AMR: 0.2773%
gnomAD_G_EAS: 0.0888%
gnomAD_G_NFE: 0.0368%
gnomAD_G_SAS: 1.1464%
INTERGENIC_VARIANT SNV 6-131903371-T-C [0|1] rs556871192
Variant score: 0.010
Transcripts:
ENPP1:ENST00000647893.1::
Pathogenicity Data:
Best Score: 0.0114476
REMM: 0.011
Frequency Data:
gnomAD_G_AFR: 0.3103%
gnomAD_G_AMR: 0.5489%
gnomAD_G_EAS: 0.1552%
gnomAD_G_NFE: 0.1377%
gnomAD_G_SAS: 0.0444%
INTERGENIC_VARIANT SNV 6-131904962-T-C [0|1] rs9375840
Variant score: 0.009
Transcripts:
ENPP1:ENST00000647893.1::
Pathogenicity Data:
Best Score: 0.0523028
REMM: 0.052
Frequency Data:
gnomAD_G_AFR: 1.9640%
gnomAD_G_AMR: 1.0496%
gnomAD_G_EAS: 0.9757%
gnomAD_G_NFE: 0.5594%
gnomAD_G_SAS: 1.0075%
INTERGENIC_VARIANT SNV 6-131906739-C-T [0/1] rs12209458
Variant score: 0.001
Transcripts:
ENPP1:ENST00000647893.1::
Pathogenicity Data:
Best Score: 0.00579405
REMM: 0.006
Frequency Data:
gnomAD_G_AFR: 1.9709%
gnomAD_G_AMR: 1.2573%
gnomAD_G_EAS: 1.1075%
gnomAD_G_NFE: 0.6789%
gnomAD_G_SAS: 1.9826%
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-131847856-G-GGTGTGT [0/1] rs59956343
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:2, B:1)
Variant score: 0.000
Transcripts:
ENPP1:ENST00000647893.1:c.313+8_313+9insGTGTGT:p.(=)
Pathogenicity Data:
Best Score: 1.0E-4
REMM: 0.000
Frequency Data:
gnomAD_E_AFR: 0.1529%
gnomAD_E_AMR: 0.5465%
gnomAD_E_EAS: 0.0869%
gnomAD_E_NFE: 0.5954%
gnomAD_E_SAS: 0.7807%
gnomAD_G_AFR: 0.4004%
gnomAD_G_AMR: 0.8063%
gnomAD_G_EAS: 0.1655%
gnomAD_G_NFE: 1.6694%
gnomAD_G_SAS: 1.5330%

RYR2

Exomiser Score: 0.124 (p=2.4E-1)

Phenotype Score: 0.502

Variant Score: 0.666

Phenotype matches:
Proximity score 0.502 in interactome to CACNA1C and phenotypic similarity 0.643 to Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures associated with CACNA1C.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Proximity score 0.502 in interactome to CACNA1C and phenotypic similarity 0.349 to mouse mutant of CACNA1C.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002759, abnormal caudal vertebrae morphology
HP:0006625, Multifocal breast carcinoma - MP:0002759, abnormal caudal vertebrae morphology
Proximity score 0.502 in interactome to CACNA1C and phenotypic similarity 0.255 to fish mutant of CACNA1C.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0001052, mandibular arch skeleton morphology, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0001052, mandibular arch skeleton morphology, abnormal
Known diseases:
OMIM:115000 Ventricular arrhythmias due to cardiac ryanodine receptor calcium release deficiency syndrome - autosomal dominant
OMIM:604772 Ventricular tachycardia, catecholaminergic polymorphic, 1 - autosomal dominant
ORPHA:3286 Catecholaminergic polymorphic ventricular tachycardia - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.124 (p=2.4E-1)

Phenotype Score: 0.502

Variant Score: 0.666

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237190295-A-T [0/1] rs1318896684
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.666 CONTRIBUTING VARIANT
Transcripts:
RYR2:ENST00000366574.7:c.49-80202A>T:p.(=)
Pathogenicity Data:
Best Score: 0.666585
REMM: 0.667
Frequency Data:
gnomAD_G_AMR: 0.0065%
gnomAD_G_NFE: 0.0015%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.010 (p=4.8E-1)

Phenotype Score: 0.251

Variant Score: 0.658

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237190295-A-T [0/1] rs1318896684
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.666 CONTRIBUTING VARIANT
Transcripts:
RYR2:ENST00000366574.7:c.49-80202A>T:p.(=)
Pathogenicity Data:
Best Score: 0.666585
REMM: 0.667
Frequency Data:
gnomAD_G_AMR: 0.0065%
gnomAD_G_NFE: 0.0015%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237594886-GTTTTTTTTTTTTTTTT-G [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.651 CONTRIBUTING VARIANT
Transcripts:
RYR2:ENST00000366574.7:c.4437-611_4437-596del:p.(=)
Pathogenicity Data:
Best Score: 0.650585
REMM: 0.651
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237562286-T-C [0/1] rs190823420
Variant score: 0.632
Transcripts:
RYR2:ENST00000366574.7:c.3215-4281T>C:p.(=)
Pathogenicity Data:
Best Score: 0.670565
REMM: 0.671
Frequency Data:
UK10K: 0.2380%
gnomAD_G_AFR: 0.0409%
gnomAD_G_AMR: 0.2810%
gnomAD_G_NFE: 0.3337%
gnomAD_G_SAS: 0.3520%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237591137-CCTCCTCCTCCCCCTCCTCCTCTTCCCCCTTCTCCTCCTCCCCCTT-C [1/1]
Variant score: 0.596
Transcripts:
RYR2:ENST00000366574.7:c.4160+146_4160+190del:p.(=)
Pathogenicity Data:
Best Score: 0.59558
REMM: 0.596
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237318896-T-G [0/1] rs150896346
Variant score: 0.552
Transcripts:
RYR2:ENST00000366574.7:c.169-11982T>G:p.(=)
Pathogenicity Data:
Best Score: 0.617052
REMM: 0.617
Frequency Data:
UK10K: 0.3703%
gnomAD_G_AFR: 0.0577%
gnomAD_G_AMR: 0.5762%
gnomAD_G_NFE: 0.3764%
gnomAD_G_SAS: 0.1453%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237221295-A-C [0/1] rs552563344
Variant score: 0.516
Transcripts:
RYR2:ENST00000366574.7:c.49-49202A>C:p.(=)
Pathogenicity Data:
Best Score: 0.539459
REMM: 0.539
Frequency Data:
UK10K: 0.2777%
gnomAD_G_AFR: 0.0313%
gnomAD_G_AMR: 0.2548%
gnomAD_G_NFE: 0.2425%
gnomAD_G_SAS: 0.1035%
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-237515730-T-TTTCTCCTCCTCGTCCTTCTCCGTCTCCTCCTTCTCCCTCTTCTCCTCCTCCCTCTTCTCCTTCTTCTCCTCCTCCCTCTTCTCCTCATCCCTTTTCTCCTCCTCCCTCTTCTCTTTCTCCCTCTTCTTCTCCCTATTCTCCTTCTCTCTG [1/1]
Variant score: 0.513
Transcripts:
RYR2:ENST00000366574.7:c.2822+3939_2822+3940insTTCTCCTCCTCGTCCTTCTCCGTCTCCTCCTTCTCCCTCTTCTCCTCCTCCCTCTTCTCCTTCTTCTCCTCCTCCCTCTTCTCCTCATCCCTTTTCTCCTCCTCCCTCTTCTCTTTCTCCCTCTTCTTCTCCCTATTCTCCTTCTCTCTG:p.(=)
Pathogenicity Data:
Best Score: 0.51253
REMM: 0.513
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-237444823-A-AAT [0/1] rs1226129326
Variant score: 0.506
Transcripts:
RYR2:ENST00000366574.7:c.1171-578_1171-577insAT:p.(=)
Pathogenicity Data:
Best Score: 0.509682
REMM: 0.510
Frequency Data:
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0131%
gnomAD_G_NFE: 0.0470%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237565016-T-C [0/1]
Variant score: 0.491
Transcripts:
RYR2:ENST00000366574.7:c.3215-1551T>C:p.(=)
Pathogenicity Data:
Best Score: 0.491312
REMM: 0.491
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237129351-A-T [0/1] rs80202103
Variant score: 0.487
Transcripts:
RYR2:ENST00000366574.7:c.48+86782A>T:p.(=)
Pathogenicity Data:
Best Score: 0.68776
REMM: 0.688
Frequency Data:
UK10K: 0.9654%
gnomAD_G_AFR: 0.1757%
gnomAD_G_AMR: 0.4768%
gnomAD_G_NFE: 1.1510%
gnomAD_G_SAS: 0.0829%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237149067-T-C [0/1] rs116682993
Variant score: 0.480
Transcripts:
RYR2:ENST00000366574.7:c.48+106498T>C:p.(=)
Pathogenicity Data:
Best Score: 0.610376
REMM: 0.610
Frequency Data:
UK10K: 0.8463%
gnomAD_G_AFR: 0.1419%
gnomAD_G_AMR: 0.4708%
gnomAD_G_NFE: 0.9453%
gnomAD_G_SAS: 0.1036%
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-237594886-G-GTTTTTTTTGTTTTTTTTTTTTTTT [0/1] rs1675642723
Variant score: 0.450
Transcripts:
RYR2:ENST00000366574.7:c.4437-612_4437-611insTTTTTTTTGTTTTTTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.454303
REMM: 0.454
Frequency Data:
gnomAD_G_NFE: 0.0183%
gnomAD_G_SAS: 0.0706%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237559448-G-A [0/1] rs114018030
Variant score: 0.448
Transcripts:
RYR2:ENST00000366574.7:c.3215-7119G>A:p.(=)
Pathogenicity Data:
Best Score: 0.551466
REMM: 0.551
Frequency Data:
UK10K: 0.3967%
gnomAD_G_AFR: 0.0650%
gnomAD_G_AMR: 0.3925%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 0.5073%
gnomAD_G_SAS: 0.8710%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237508734-CTT-C [1/1] rs869044432
Variant score: 0.443
Transcripts:
RYR2:ENST00000366574.7:c.2718+1921_2718+1922del:p.(=)
Pathogenicity Data:
Best Score: 0.443465
REMM: 0.443
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237157295-CAAAAAAA-C [0/1]
Variant score: 0.420
Transcripts:
RYR2:ENST00000366574.7:c.49-113201_49-113195del:p.(=)
Pathogenicity Data:
Best Score: 0.420171
REMM: 0.420
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237423917-C-G [0/1] rs1323160823
Variant score: 0.412
Transcripts:
RYR2:ENST00000366574.7:c.1005+669C>G:p.(=)
Pathogenicity Data:
Best Score: 0.411979
REMM: 0.412
Frequency Data:
gnomAD_G_NFE: 0.0015%
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-237805580-C-CAAA [0/1]
Variant score: 0.408
Transcripts:
RYR2:ENST00000366574.7:c.14152-557_14152-556insAAA:p.(=)
Pathogenicity Data:
Best Score: 0.407843
REMM: 0.408
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 1-237030645-A-G [0/1] rs146271345
Variant score: 0.407
Transcripts:
RYR2:ENST00000366574.7::
Pathogenicity Data:
Best Score: 0.681163
REMM: 0.681
Frequency Data:
UK10K: 0.7009%
gnomAD_G_AFR: 0.1709%
gnomAD_G_AMR: 1.3800%
gnomAD_G_NFE: 0.9232%
gnomAD_G_SAS: 0.0622%
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-237230927-C-CAAAAAAAAAAA [1/1]
Variant score: 0.394
Transcripts:
RYR2:ENST00000366574.7:c.49-39570_49-39569insAAAAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.393873
REMM: 0.394
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237105834-CA-C [0/1]
Variant score: 0.364
Transcripts:
RYR2:ENST00000366574.7:c.48+63266del:p.(=)
Pathogenicity Data:
Best Score: 0.364422
REMM: 0.364
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237064751-CTTTTTTTT-C [1|1] rs551797601
Variant score: 0.316
Transcripts:
RYR2:ENST00000366574.7:c.48+22183_48+22190del:p.(=)
Pathogenicity Data:
Best Score: 0.315523
REMM: 0.316
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237157295-CA-C [0/1]
Variant score: 0.306
Transcripts:
RYR2:ENST00000366574.7:c.49-113201del:p.(=)
Pathogenicity Data:
Best Score: 0.306427
REMM: 0.306
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237178416-CTGTGTGTGTGTGTGTGTGTGTGTG-C [0/1] rs201867544
Variant score: 0.294
Transcripts:
RYR2:ENST00000366574.7:c.49-92080_49-92057del:p.(=)
Pathogenicity Data:
Best Score: 0.348078
REMM: 0.348
Frequency Data:
gnomAD_G_AFR: 0.0620%
gnomAD_G_AMR: 0.7647%
gnomAD_G_EAS: 0.0233%
gnomAD_G_NFE: 0.1475%
gnomAD_G_SAS: 0.0582%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237546993-ATATT-A [0/1] rs71180099
Variant score: 0.284
Transcripts:
RYR2:ENST00000366574.7:c.2907-1437_2907-1434del:p.(=)
Pathogenicity Data:
Best Score: 0.291538
REMM: 0.292
Frequency Data:
gnomAD_G_AFR: 0.1720%
gnomAD_G_AMR: 0.0765%
gnomAD_G_EAS: 0.1414%
gnomAD_G_NFE: 0.0246%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237397111-C-T [0/1] rs187676555
Variant score: 0.283
Transcripts:
RYR2:ENST00000366574.7:c.773+8928C>T:p.(=)
Pathogenicity Data:
Best Score: 0.394005
REMM: 0.394
Frequency Data:
UK10K: 1.1240%
gnomAD_G_AFR: 0.2607%
gnomAD_G_AMR: 1.0552%
gnomAD_G_NFE: 1.0661%
gnomAD_G_SAS: 0.1666%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237591204-C-T [0/1] rs113768697
Variant score: 0.283
Transcripts:
RYR2:ENST00000366574.7:c.4160+212C>T:p.(=)
Pathogenicity Data:
Best Score: 0.282614
REMM: 0.283
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237123650-ATT-A [1/1] rs869177997
Variant score: 0.253
Transcripts:
RYR2:ENST00000366574.7:c.48+81082_48+81083del:p.(=)
Pathogenicity Data:
Best Score: 0.252833
REMM: 0.253
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 1-237025029-G-C [1/1] rs12730339
Variant score: 0.252
Transcripts:
RYR2:ENST00000366574.7::
Pathogenicity Data:
Best Score: 0.251958
REMM: 0.252
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 1-237024783-A-G [1/1] rs571695742
Variant score: 0.249
Transcripts:
RYR2:ENST00000366574.7::
Pathogenicity Data:
Best Score: 0.249124
REMM: 0.249
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237579248-CTT-C [1/1]
Variant score: 0.242
Transcripts:
RYR2:ENST00000366574.7:c.3598+9930_3598+9931del:p.(=)
Pathogenicity Data:
Best Score: 0.241925
REMM: 0.242
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 1-237025325-C-T [1/1] rs12404423
Variant score: 0.231
Transcripts:
RYR2:ENST00000366574.7::
Pathogenicity Data:
Best Score: 0.231079
REMM: 0.231
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237628374-C-T [0/1] rs477075
ClinVar: BENIGN (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.223
Transcripts:
RYR2:ENST00000366574.7:c.6440+294C>T:p.(=)
Pathogenicity Data:
Best Score: 0.223267
REMM: 0.223
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237045869-GTTTTT-G [0/1] rs768636054
Variant score: 0.210
Transcripts:
RYR2:ENST00000366574.7:c.48+3301_48+3305del:p.(=)
Pathogenicity Data:
Best Score: 0.210394
REMM: 0.210
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237075468-T-C [1/1] rs3011689
Variant score: 0.206
Transcripts:
RYR2:ENST00000366574.7:c.48+32899T>C:p.(=)
Pathogenicity Data:
Best Score: 0.205623
REMM: 0.206
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-237402825-A-AGGG [0|1] rs879867135
Variant score: 0.201
Transcripts:
RYR2:ENST00000366574.7:c.774-14224_774-14223insGGG:p.(=)
Pathogenicity Data:
Best Score: 0.201234
REMM: 0.201
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237714990-TCAAAAAA-T [0/1] rs1689142820
Variant score: 0.200
Transcripts:
RYR2:ENST00000366574.7:c.10324-2207_10324-2201del:p.(=)
Pathogenicity Data:
Best Score: 0.199573
REMM: 0.200
Frequency Data:
gnomAD_G_NFE: 0.0019%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237402838-GCGGT-G [0|1] rs1404819190
Variant score: 0.185
Transcripts:
RYR2:ENST00000366574.7:c.774-14210_774-14207del:p.(=)
Pathogenicity Data:
Best Score: 0.184524
REMM: 0.185
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237714990-TCAA-T [0/1] rs1193271780
Variant score: 0.184
Transcripts:
RYR2:ENST00000366574.7:c.10324-2207_10324-2205del:p.(=)
Pathogenicity Data:
Best Score: 0.184242
REMM: 0.184
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237075637-TCGCGCTGATTG-T [0/1]
Variant score: 0.181
Transcripts:
RYR2:ENST00000366574.7:c.48+33069_48+33079del:p.(=)
Pathogenicity Data:
Best Score: 0.180975
REMM: 0.181
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237714998-A-T [0/1] rs1230540774
Variant score: 0.179
Transcripts:
RYR2:ENST00000366574.7:c.10324-2200A>T:p.(=)
Pathogenicity Data:
Best Score: 0.179004
REMM: 0.179
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-237402830-G-GGTTT [0|1] rs1357244569
Variant score: 0.177
Transcripts:
RYR2:ENST00000366574.7:c.774-14219_774-14218insGTTT:p.(=)
Pathogenicity Data:
Best Score: 0.177212
REMM: 0.177
Frequency Data:
No frequency data
THREE_PRIME_UTR_EXON_VARIANT INS 1-237833351-G-GC [0/1] rs397983403
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.172
Transcripts:
RYR2:ENST00000366574.7:c.*716dup:p.(=)
Pathogenicity Data:
Best Score: 0.742364
REMM: 0.742
Frequency Data:
gnomAD_G_AFR: 1.5427%
gnomAD_G_AMR: 0.5866%
gnomAD_G_EAS: 1.8991%
gnomAD_G_NFE: 0.3472%
gnomAD_G_SAS: 0.8579%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237427782-CAAAA-C [0/1]
Variant score: 0.164
Transcripts:
RYR2:ENST00000366574.7:c.1005+4535_1005+4538del:p.(=)
Pathogenicity Data:
Best Score: 0.164231
REMM: 0.164
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237278245-AT-A [0/1] rs71561863
Variant score: 0.160
Transcripts:
RYR2:ENST00000366574.7:c.168+7630del:p.(=)
Pathogenicity Data:
Best Score: 0.160062
REMM: 0.160
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-237193167-C-CAAAAAAAAAAAAAA [1/1]
Variant score: 0.155
Transcripts:
RYR2:ENST00000366574.7:c.49-77330_49-77329insAAAAAAAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.155332
REMM: 0.155
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 1-237024376-AT-A [1/1]
Variant score: 0.147
Transcripts:
RYR2:ENST00000366574.7::
Pathogenicity Data:
Best Score: 0.146654
REMM: 0.147
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 1-237024116-C-T [1/1]
Variant score: 0.145
Transcripts:
RYR2:ENST00000366574.7::
Pathogenicity Data:
Best Score: 0.145215
REMM: 0.145
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237827936-CA-C [0/1]
Variant score: 0.129
Transcripts:
RYR2:ENST00000366574.7:c.14591-444del:p.(=)
Pathogenicity Data:
Best Score: 0.128771
REMM: 0.129
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237395533-CTTTTTTTTTTT-C [0/1] rs71180022
Variant score: 0.120
Transcripts:
RYR2:ENST00000366574.7:c.773+7351_773+7361del:p.(=)
Pathogenicity Data:
Best Score: 0.120139
REMM: 0.120
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237395533-CTTTTTTTTTTTT-C [0/1] rs71180022
Variant score: 0.120
Transcripts:
RYR2:ENST00000366574.7:c.773+7351_773+7362del:p.(=)
Pathogenicity Data:
Best Score: 0.120139
REMM: 0.120
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237542062-ATTTATTTATTTATTTATT-A [0|1]
Variant score: 0.119
Transcripts:
RYR2:ENST00000366574.7:c.2907-6368_2907-6351del:p.(=)
Pathogenicity Data:
Best Score: 0.119006
REMM: 0.119
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 1-237024543-C-T [1/1] rs201504528
Variant score: 0.113
Transcripts:
RYR2:ENST00000366574.7::
Pathogenicity Data:
Best Score: 0.112673
REMM: 0.113
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237262245-GTT-G [0/1]
Variant score: 0.105
Transcripts:
RYR2:ENST00000366574.7:c.49-8251_49-8250del:p.(=)
Pathogenicity Data:
Best Score: 0.105316
REMM: 0.105
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-237107519-C-CAAAAAAAAAAAAA [0/1]
Variant score: 0.099
Transcripts:
RYR2:ENST00000366574.7:c.48+64950_48+64951insAAAAAAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.098844
REMM: 0.099
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-237107519-C-CAAAAAAAAAAAAAAA [0/1]
Variant score: 0.099
Transcripts:
RYR2:ENST00000366574.7:c.48+64950_48+64951insAAAAAAAAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.098844
REMM: 0.099
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237075639-G-T [1/1] rs6428988
Variant score: 0.095
Transcripts:
RYR2:ENST00000366574.7:c.48+33070G>T:p.(=)
Pathogenicity Data:
Best Score: 0.0945246
REMM: 0.095
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-237697598-A-AT [0/1] rs199830480
Variant score: 0.091
Transcripts:
RYR2:ENST00000366574.7:c.9068-1367_9068-1366insT:p.(=)
Pathogenicity Data:
Best Score: 0.1667
REMM: 0.167
Frequency Data:
gnomAD_G_AFR: 1.4732%
gnomAD_G_AMR: 0.2295%
gnomAD_G_EAS: 0.0631%
gnomAD_G_NFE: 0.0907%
gnomAD_G_SAS: 0.1141%
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-237061276-C-CT [1/1] rs1553275503
Variant score: 0.089
Transcripts:
RYR2:ENST00000366574.7:c.48+18707_48+18708insT:p.(=)
Pathogenicity Data:
Best Score: 0.0888008
REMM: 0.089
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 1-237024940-C-T [0/1]
Variant score: 0.088
Transcripts:
RYR2:ENST00000366574.7::
Pathogenicity Data:
Best Score: 0.087956
REMM: 0.088
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237538394-CAA-C [0/1] rs10551995
Variant score: 0.086
Transcripts:
RYR2:ENST00000366574.7:c.2906+7885_2906+7886del:p.(=)
Pathogenicity Data:
Best Score: 0.0861139
REMM: 0.086
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237538394-CAAAA-C [0/1] rs10551995
Variant score: 0.086
Transcripts:
RYR2:ENST00000366574.7:c.2906+7885_2906+7888del:p.(=)
Pathogenicity Data:
Best Score: 0.0861139
REMM: 0.086
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-237248267-A-AC [1|1]
Variant score: 0.084
Transcripts:
RYR2:ENST00000366574.7:c.49-22230_49-22229insC:p.(=)
Pathogenicity Data:
Best Score: 0.0835972
REMM: 0.084
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237076013-C-T [0/1] rs10155576
Variant score: 0.084
Transcripts:
RYR2:ENST00000366574.7:c.48+33444C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0835123
REMM: 0.084
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 1-237025245-T-C [1/1] rs4250125
Variant score: 0.078
Transcripts:
RYR2:ENST00000366574.7::
Pathogenicity Data:
Best Score: 0.0781278
REMM: 0.078
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 1-237025213-A-G [1/1] rs12095817
Variant score: 0.075
Transcripts:
RYR2:ENST00000366574.7::
Pathogenicity Data:
Best Score: 0.0745139
REMM: 0.075
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-237473442-T-TTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTC [0/1] rs1553464684
Variant score: 0.067
Transcripts:
RYR2:ENST00000366574.7:c.1708+4255_1708+4256insTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTC:p.(=)
Pathogenicity Data:
Best Score: 0.0665111
REMM: 0.067
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-237473442-T-TTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTC [0/1] rs1553464684
Variant score: 0.062
Transcripts:
RYR2:ENST00000366574.7:c.1708+4255_1708+4256insTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTTCTTC:p.(=)
Pathogenicity Data:
Best Score: 0.0665111
REMM: 0.067
Frequency Data:
gnomAD_G_AMR: 0.0219%
gnomAD_G_EAS: 0.4087%
gnomAD_G_NFE: 0.0427%
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-237240665-C-CAA [0/1]
Variant score: 0.056
Transcripts:
RYR2:ENST00000366574.7:c.49-29832_49-29831insAA:p.(=)
Pathogenicity Data:
Best Score: 0.0555817
REMM: 0.056
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-237240665-C-CAAA [0/1]
Variant score: 0.056
Transcripts:
RYR2:ENST00000366574.7:c.49-29832_49-29831insAAA:p.(=)
Pathogenicity Data:
Best Score: 0.0555817
REMM: 0.056
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237045869-GT-G [0/1] rs768636054
Variant score: 0.050
Transcripts:
RYR2:ENST00000366574.7:c.48+3301del:p.(=)
Pathogenicity Data:
Best Score: 0.0499353
REMM: 0.050
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-237536714-C-CAA [1/1] rs71561885
Variant score: 0.040
Transcripts:
RYR2:ENST00000366574.7:c.2906+6204_2906+6205insAA:p.(=)
Pathogenicity Data:
Best Score: 0.0399294
REMM: 0.040
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237075615-A-G [1/1] rs530586322
Variant score: 0.035
Transcripts:
RYR2:ENST00000366574.7:c.48+33046A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0350782
REMM: 0.035
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237565163-CTTTCTT-C [0|1]
Variant score: 0.027
Transcripts:
RYR2:ENST00000366574.7:c.3215-1403_3215-1398del:p.(=)
Pathogenicity Data:
Best Score: 0.0270548
REMM: 0.027
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-237402872-C-CACCG [1|1] rs1329337353
Variant score: 0.027
Transcripts:
RYR2:ENST00000366574.7:c.774-14177_774-14176insACCG:p.(=)
Pathogenicity Data:
Best Score: 0.0269373
REMM: 0.027
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-237626580-C-CT [0/1] rs60885998
Variant score: 0.021
Transcripts:
RYR2:ENST00000366574.7:c.6166+776_6166+777insT:p.(=)
Pathogenicity Data:
Best Score: 0.0212722
REMM: 0.021
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT INS 1-237039550-A-AT [0/1] rs111484491
Variant score: 0.019
Transcripts:
RYR2:ENST00000366574.7::
Pathogenicity Data:
Best Score: 0.0422444
REMM: 0.042
Frequency Data:
gnomAD_G_AFR: 0.7903%
gnomAD_G_AMR: 0.9299%
gnomAD_G_EAS: 0.1801%
gnomAD_G_NFE: 1.6200%
gnomAD_G_SAS: 1.2174%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237565121-TTC-T [1|1]
Variant score: 0.016
Transcripts:
RYR2:ENST00000366574.7:c.3215-1445_3215-1444del:p.(=)
Pathogenicity Data:
Best Score: 0.016404
REMM: 0.016
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237628400-C-G [0/1] rs476971
Variant score: 0.014
Transcripts:
RYR2:ENST00000366574.7:c.6440+320C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0137048
REMM: 0.014
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237076732-C-A [1/1] rs199943473
Variant score: 0.014
Transcripts:
RYR2:ENST00000366574.7:c.48+34163C>A:p.(=)
Pathogenicity Data:
Best Score: 0.0136202
REMM: 0.014
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237077160-T-G [1/1]
Variant score: 0.011
Transcripts:
RYR2:ENST00000366574.7:c.48+34591T>G:p.(=)
Pathogenicity Data:
Best Score: 0.0109813
REMM: 0.011
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237078168-A-G [0/1] rs11485013
Variant score: 0.010
Transcripts:
RYR2:ENST00000366574.7:c.48+35599A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0103377
REMM: 0.010
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237076500-C-T [1/1] rs201826146
Variant score: 0.010
Transcripts:
RYR2:ENST00000366574.7:c.48+33931C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0103008
REMM: 0.010
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237080603-C-T [1|1] rs56102712
Variant score: 0.010
Transcripts:
RYR2:ENST00000366574.7:c.48+38034C>T:p.(=)
Pathogenicity Data:
Best Score: 0.009975
REMM: 0.010
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237080608-G-A [1|1] rs56114377
Variant score: 0.008
Transcripts:
RYR2:ENST00000366574.7:c.48+38039G>A:p.(=)
Pathogenicity Data:
Best Score: 0.008175
REMM: 0.008
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237077457-A-G [0/1]
Variant score: 0.008
Transcripts:
RYR2:ENST00000366574.7:c.48+34888A>G:p.(=)
Pathogenicity Data:
Best Score: 0.00790833
REMM: 0.008
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237077437-T-C [0/1] rs11810433
Variant score: 0.007
Transcripts:
RYR2:ENST00000366574.7:c.48+34868T>C:p.(=)
Pathogenicity Data:
Best Score: 0.00735278
REMM: 0.007
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-237237945-C-CTTT [0/1] rs144453604
Variant score: 0.007
Transcripts:
RYR2:ENST00000366574.7:c.49-32552_49-32551insTTT:p.(=)
Pathogenicity Data:
Best Score: 0.00722341
REMM: 0.007
Frequency Data:
gnomAD_G_AFR: 0.0129%
gnomAD_G_AMR: 0.0452%
gnomAD_G_NFE: 0.0073%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237094334-G-A [0/1] rs368290406
Variant score: 0.006
Transcripts:
RYR2:ENST00000366574.7:c.48+51765G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00657063
REMM: 0.007
Frequency Data:
UK10K: 0.1058%
gnomAD_G_AFR: 0.0313%
gnomAD_G_AMR: 0.0392%
gnomAD_G_NFE: 0.1676%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237078806-T-C [1/1] rs75035402
Variant score: 0.006
Transcripts:
RYR2:ENST00000366574.7:c.48+36237T>C:p.(=)
Pathogenicity Data:
Best Score: 0.00628611
REMM: 0.006
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237079973-C-T [1/1] rs61831902
Variant score: 0.006
Transcripts:
RYR2:ENST00000366574.7:c.48+37404C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00578611
REMM: 0.006
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237080967-C-G [1/1]
Variant score: 0.006
Transcripts:
RYR2:ENST00000366574.7:c.48+38398C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0056373
REMM: 0.006
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237350617-A-C [0/1] rs865881591
Variant score: 0.005
Transcripts:
RYR2:ENST00000366574.7:c.274-5348A>C:p.(=)
Pathogenicity Data:
Best Score: 0.00515794
REMM: 0.005
Frequency Data:
gnomAD_G_AFR: 0.0752%
gnomAD_G_AMR: 0.1167%
gnomAD_G_NFE: 0.4423%
gnomAD_G_SAS: 0.0267%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237319445-A-G [0/1] rs72765924
Variant score: 0.004
Transcripts:
RYR2:ENST00000366574.7:c.169-11433A>G:p.(=)
Pathogenicity Data:
Best Score: 0.00820556
REMM: 0.008
Frequency Data:
UK10K: 1.2695%
gnomAD_G_AFR: 0.2118%
gnomAD_G_AMR: 0.9812%
gnomAD_G_EAS: 0.0579%
gnomAD_G_NFE: 1.5631%
gnomAD_G_SAS: 0.2900%
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-237795873-T-TATGTATATGTATATATATATATATAC [0/1] rs140571706
Variant score: 0.003
Transcripts:
RYR2:ENST00000366574.7:c.13956+542_13956+543insATGTATATGTATATATATATATATAC:p.(=)
Pathogenicity Data:
Best Score: 0.00337738
REMM: 0.003
Frequency Data:
gnomAD_G_AFR: 0.0350%
gnomAD_G_AMR: 0.1831%
gnomAD_G_NFE: 0.1890%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237107337-C-T [0/1] rs566559116
Variant score: 0.002
Transcripts:
RYR2:ENST00000366574.7:c.48+64768C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00273175
REMM: 0.003
Frequency Data:
gnomAD_G_AFR: 0.2500%
gnomAD_G_AMR: 0.6275%
gnomAD_G_EAS: 0.0196%
gnomAD_G_NFE: 1.0726%
gnomAD_G_SAS: 0.7216%
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-237623386-T-TCTTTCTTTCTTTC [0/1]
Variant score: 0.002
Transcripts:
RYR2:ENST00000366574.7:c.5917-379_5917-378insCTTTCTTTCTTTC:p.(=)
Pathogenicity Data:
Best Score: 0.00150119
REMM: 0.002
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237591197-T-C [0/1]
Variant score: 0.001
Transcripts:
RYR2:ENST00000366574.7:c.4160+205T>C:p.(=)
Pathogenicity Data:
Best Score: 0.00142857
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-237303292-C-CT [0/1] rs386370109
Variant score: 0.001
Transcripts:
RYR2:ENST00000366574.7:c.169-27586_169-27585insT:p.(=)
Pathogenicity Data:
Best Score: 0.00111111
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237509131-A-G [0/1] rs890060331
Variant score: 0.001
Transcripts:
RYR2:ENST00000366574.7:c.2718+2317A>G:p.(=)
Pathogenicity Data:
Best Score: 0.001
REMM: 0.001
Frequency Data:
gnomAD_G_NFE: 0.0015%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237557204-A-G [0/1] rs115391058
Variant score: 0.001
Transcripts:
RYR2:ENST00000366574.7:c.3214+6513A>G:p.(=)
Pathogenicity Data:
Best Score: 8.88889E-4
REMM: 0.001
Frequency Data:
UK10K: 0.2777%
gnomAD_G_AFR: 0.1082%
gnomAD_G_AMR: 0.5232%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 0.4822%
gnomAD_G_SAS: 0.0414%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237395119-G-T [0/1] rs140263733
Variant score: 0.001
Transcripts:
RYR2:ENST00000366574.7:c.773+6936G>T:p.(=)
Pathogenicity Data:
Best Score: 0.001
REMM: 0.001
Frequency Data:
UK10K: 1.1373%
gnomAD_G_AFR: 0.2744%
gnomAD_G_AMR: 1.1642%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.4554%
gnomAD_G_SAS: 0.1456%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237814965-CT-C [0/1]
Variant score: 0.001
Transcripts:
RYR2:ENST00000366574.7:c.14434-4070del:p.(=)
Pathogenicity Data:
Best Score: 5.33333E-4
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237513445-C-T [0/1] rs528671549
Variant score: 0.000
Transcripts:
RYR2:ENST00000366574.7:c.2822+1654C>T:p.(=)
Pathogenicity Data:
Best Score: 3.33333E-4
REMM: 0.000
Frequency Data:
gnomAD_G_NFE: 0.0015%
gnomAD_G_SAS: 0.0415%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-237383417-GT-G [0/1]
Variant score: 0.000
Transcripts:
RYR2:ENST00000366574.7:c.577-3863del:p.(=)
Pathogenicity Data:
Best Score: 1.25E-4
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237506401-A-G [0|1] rs181278300
Variant score: 0.000
Transcripts:
RYR2:ENST00000366574.7:c.2614-309A>G:p.(=)
Pathogenicity Data:
Best Score: 1.95695E-6
REMM: 0.000
Frequency Data:
UK10K: 0.3835%
gnomAD_G_AFR: 0.0699%
gnomAD_G_AMR: 0.3469%
gnomAD_G_NFE: 0.4897%
gnomAD_G_SAS: 0.8302%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237091429-G-T [1|1] rs6686489
Variant score: 0.000
Transcripts:
RYR2:ENST00000366574.7:c.48+48860G>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237091430-G-T [1|1] rs6686490
Variant score: 0.000
Transcripts:
RYR2:ENST00000366574.7:c.48+48861G>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237252054-C-T [0/1] rs181654259
Variant score: 0.000
Transcripts:
RYR2:ENST00000366574.7:c.49-18443C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.1058%
gnomAD_G_AFR: 0.0410%
gnomAD_G_AMR: 0.5177%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 0.1632%
gnomAD_G_SAS: 0.0208%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237302549-C-T [0/1] rs147560698
Variant score: 0.000
Transcripts:
RYR2:ENST00000366574.7:c.169-28329C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.1190%
gnomAD_G_AMR: 0.0262%
gnomAD_G_NFE: 0.0323%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237312364-C-G [0/1]
Variant score: 0.000
Transcripts:
RYR2:ENST00000366574.7:c.169-18514C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237344625-G-A [0/1] rs538963993
Variant score: 0.000
Transcripts:
RYR2:ENST00000366574.7:c.274-11340G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0386%
gnomAD_G_AMR: 0.0262%
gnomAD_G_NFE: 0.0029%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237434650-C-T [0/1] rs115159727
Variant score: 0.000
Transcripts:
RYR2:ENST00000366574.7:c.1006-6669C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.1769%
gnomAD_G_AFR: 0.3081%
gnomAD_G_AMR: 1.0597%
gnomAD_G_EAS: 0.0386%
gnomAD_G_NFE: 1.6203%
gnomAD_G_SAS: 0.1247%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-237473463-A-T [1/1] rs12046814
Variant score: 0.000
Transcripts:
RYR2:ENST00000366574.7:c.1708+4276A>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data

MADD

Exomiser Score: 0.124 (p=2.4E-1)

Phenotype Score: 0.582

Variant Score: 0.575

Phenotype matches:
Phenotypic similarity 0.582 to DEEAH syndrome associated with MADD.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0006610, Wide intermamillary distance
HP:0006625, Multifocal breast carcinoma - HP:0006610, Wide intermamillary distance
Known diseases:
OMIM:619004 DEEAH syndrome - autosomal recessive
OMIM:619005 Neurodevelopmental disorder with dysmorphic facies, impaired speech and hypotonia - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.124 (p=2.4E-1)

Phenotype Score: 0.582

Variant Score: 0.575

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.582 to OMIM:619004 DEEAH syndrome
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 11-47318789-ATTTTTTTTTTTTTTTT-A [0/1] rs57548484
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.603 CONTRIBUTING VARIANT
Transcripts:
MADD:ENST00000706887.1:c.4377+3463_4377+3478del:p.(=)
Pathogenicity Data:
Best Score: 0.603464
REMM: 0.603
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 11-47317383-G-A [0/1] rs192432527
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.546 CONTRIBUTING VARIANT
Transcripts:
MADD:ENST00000706887.1:c.4377+2056G>A:p.(=)
Pathogenicity Data:
Best Score: 0.65178
REMM: 0.652
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AFR: 0.0072%
gnomAD_G_AMR: 0.0719%
gnomAD_G_NFE: 0.0147%
gnomAD_G_SAS: 0.7881%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.000 (p=8.1E-1)

Phenotype Score: 0.000

Variant Score: 0.603

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 11-47318789-ATTTTTTTTTTTTTTTT-A [0/1] rs57548484
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.603 CONTRIBUTING VARIANT
Transcripts:
MADD:ENST00000706887.1:c.4377+3463_4377+3478del:p.(=)
Pathogenicity Data:
Best Score: 0.603464
REMM: 0.603
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 11-47317944-GT-G [0/1] rs535391980
Variant score: 0.350
Transcripts:
MADD:ENST00000706887.1:c.4377+2618del:p.(=)
Pathogenicity Data:
Best Score: 0.418133
REMM: 0.418
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AMR: 0.0591%
gnomAD_G_NFE: 0.0147%
gnomAD_G_SAS: 0.7903%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 11-47303239-GT-G [0/1] rs35658298
Variant score: 0.097
Transcripts:
MADD:ENST00000706887.1:c.3760-5351del:p.(=)
Pathogenicity Data:
Best Score: 0.09725
REMM: 0.097
Frequency Data:
No frequency data
SYNONYMOUS_VARIANT SNV 11-47329084-G-T [0/1] rs184207033
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:1, LB:1)
Variant score: 0.084
Transcripts:
MADD:ENST00000706887.1:c.4887G>T:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 0.0090%
gnomAD_E_AMR: 0.0626%
gnomAD_E_NFE: 0.0192%
gnomAD_E_SAS: 0.6967%
gnomAD_G_AMR: 0.0588%
gnomAD_G_NFE: 0.0176%
gnomAD_G_SAS: 0.7884%
CODING_TRANSCRIPT_INTRON_VARIANT INS 11-47299585-C-CT [0/1] rs1185948034
Variant score: 0.074
Transcripts:
MADD:ENST00000706887.1:c.3759+3530_3759+3531insT:p.(=)
Pathogenicity Data:
Best Score: 0.139017
REMM: 0.139
Frequency Data:
gnomAD_G_AFR: 1.4890%
gnomAD_G_AMR: 0.5090%
gnomAD_G_EAS: 0.5938%
gnomAD_G_NFE: 0.9117%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 11-47314631-C-T [0/1] rs535365125
Variant score: 0.004
Transcripts:
MADD:ENST00000706887.1:c.4270-589C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00576587
REMM: 0.006
Frequency Data:
UK10K: 0.1322%
gnomAD_G_AFR: 0.0458%
gnomAD_G_AMR: 0.2813%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.2427%
gnomAD_G_SAS: 1.2448%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 11-47287782-AT-A [1/1] rs57417064
Variant score: 0.002
Transcripts:
MADD:ENST00000706887.1:c.2654-1185del:p.(=)
Pathogenicity Data:
Best Score: 0.00194444
REMM: 0.002
Frequency Data:
No frequency data

SMAD9

Exomiser Score: 0.122 (p=2.5E-1)

Phenotype Score: 0.503

Variant Score: 0.662

Phenotype matches:
Proximity score 0.503 in interactome to TGFBR2 and phenotypic similarity 0.998 to Lynch syndrome associated with TGFBR2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.503 in interactome to TGFBR2 and phenotypic similarity 0.368 to mouse mutant of TGFBR2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000160, kyphosis
HP:0006625, Multifocal breast carcinoma - MP:0000160, kyphosis
Known diseases:
OMIM:615342 Pulmonary hypertension, primary, 2 - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.122 (p=2.5E-1)

Phenotype Score: 0.503

Variant Score: 0.662

No phenotype matches to diseases with this MOI.
Variants contributing to score:
FIVE_PRIME_UTR_INTRON_VARIANT SNV 13-36900001-C-T [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.662 CONTRIBUTING VARIANT
Transcripts:
SMAD9:ENST00000379826.5:c.-187+20115G>A:p.(=)
Pathogenicity Data:
Best Score: 0.661933
REMM: 0.662
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.009 (p=4.9E-1)

Phenotype Score: 0.252

Variant Score: 0.645

No phenotype matches to diseases with this MOI.
Variants contributing to score:
FIVE_PRIME_UTR_INTRON_VARIANT SNV 13-36900001-C-T [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.662 CONTRIBUTING VARIANT
Transcripts:
SMAD9:ENST00000379826.5:c.-187+20115G>A:p.(=)
Pathogenicity Data:
Best Score: 0.661933
REMM: 0.662
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT INS 13-36887040-G-GTT [0/1] rs200264324
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.628 CONTRIBUTING VARIANT
Transcripts:
SMAD9:ENST00000379826.5:c.-186-7166_-186-7165insAA:p.(=)
Pathogenicity Data:
Best Score: 0.627934
REMM: 0.628
Frequency Data:
No frequency data
Other passed variants:
FIVE_PRIME_UTR_INTRON_VARIANT INS 13-36887040-G-GT [0/1] rs200264324
Variant score: 0.628
Transcripts:
SMAD9:ENST00000379826.5:c.-186-7166_-186-7165insA:p.(=)
Pathogenicity Data:
Best Score: 0.627934
REMM: 0.628
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT INS 13-36896109-G-GTATT [0/1] rs57024507
Variant score: 0.585
Transcripts:
SMAD9:ENST00000379826.5:c.-186-16235_-186-16234insAATA:p.(=)
Pathogenicity Data:
Best Score: 0.584867
REMM: 0.585
Frequency Data:
No frequency data
DOWNSTREAM_GENE_VARIANT SNV 13-36840331-T-A [1/1] rs375802737
Variant score: 0.552
Transcripts:
SMAD9:ENST00000379826.5::
Pathogenicity Data:
Best Score: 0.552444
REMM: 0.552
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT INS 13-36911615-T-TG [0/1]
Variant score: 0.471
Transcripts:
SMAD9:ENST00000379826.5:c.-187+8500_-187+8501insC:p.(=)
Pathogenicity Data:
Best Score: 0.470948
REMM: 0.471
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT DEL 13-36905774-CAAAAAAA-C [0/1]
Variant score: 0.455
Transcripts:
SMAD9:ENST00000379826.5:c.-187+14335_-187+14341del:p.(=)
Pathogenicity Data:
Best Score: 0.455027
REMM: 0.455
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT DEL 13-36905774-CAAAAAAAAAAAAAA-C [0/1]
Variant score: 0.455
Transcripts:
SMAD9:ENST00000379826.5:c.-187+14328_-187+14341del:p.(=)
Pathogenicity Data:
Best Score: 0.455027
REMM: 0.455
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT DEL 13-36897849-CTT-C [0/1] rs574741770
Variant score: 0.448
Transcripts:
SMAD9:ENST00000379826.5:c.-186-17976_-186-17975del:p.(=)
Pathogenicity Data:
Best Score: 0.448407
REMM: 0.448
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 13-36874854-CAAAA-C [0/1] rs529721275
Variant score: 0.341
Transcripts:
SMAD9:ENST00000379826.5:c.413-1943_413-1940del:p.(=)
Pathogenicity Data:
Best Score: 0.388388
REMM: 0.388
Frequency Data:
gnomAD_G_AFR: 0.6408%
gnomAD_G_AMR: 0.1775%
gnomAD_G_EAS: 0.0858%
gnomAD_G_NFE: 0.2124%
gnomAD_G_SAS: 0.1311%
FIVE_PRIME_UTR_INTRON_VARIANT DEL 13-36887214-CT-C [0/1] rs34299786
Variant score: 0.195
Transcripts:
SMAD9:ENST00000379826.5:c.-186-7340del:p.(=)
Pathogenicity Data:
Best Score: 0.195107
REMM: 0.195
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT DEL 13-36887214-CTTT-C [0/1] rs34299786
Variant score: 0.195
Transcripts:
SMAD9:ENST00000379826.5:c.-186-7342_-186-7340del:p.(=)
Pathogenicity Data:
Best Score: 0.195107
REMM: 0.195
Frequency Data:
No frequency data

TBX3

Exomiser Score: 0.118 (p=2.5E-1)

Phenotype Score: 0.590

Variant Score: 0.560

Phenotype matches:
Phenotypic similarity 0.590 to Ulnar-mammary syndrome associated with TBX3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Phenotypic similarity 0.299 to mouse mutant involving TBX3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0004509, abnormal pelvic girdle bone morphology
HP:0006625, Multifocal breast carcinoma - MP:0004509, abnormal pelvic girdle bone morphology
Proximity score 0.502 in interactome to CDKN2A and phenotypic similarity 0.998 to Familial pancreatic carcinoma associated with CDKN2A.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.502 in interactome to CDKN2A and phenotypic similarity 0.290 to mouse mutant of CDKN2A.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0003789, increased osteosarcoma incidence
HP:0006625, Multifocal breast carcinoma - MP:0003789, increased osteosarcoma incidence
Known diseases:
OMIM:181450 Ulnar-mammary syndrome - autosomal dominant
ORPHA:3138 Ulnar-mammary syndrome - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.118 (p=2.5E-1)

Phenotype Score: 0.590

Variant Score: 0.560

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.590 to OMIM:181450 Ulnar-mammary syndrome
Phenotypic similarity 0.587 to ORPHA:3138 Ulnar-mammary syndrome
Variants contributing to score:
DOWNSTREAM_GENE_VARIANT INS 12-114665427-C-CCCA [0/1] rs1555242989
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.560 CONTRIBUTING VARIANT
Transcripts:
TBX3:ENST00000349155.7::
Pathogenicity Data:
Best Score: 0.560138
REMM: 0.560
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.004 (p=5.7E-1)

Phenotype Score: 0.251

Variant Score: 0.560

No phenotype matches to diseases with this MOI.
Variants contributing to score:
DOWNSTREAM_GENE_VARIANT INS 12-114665427-C-CCA [0/1] rs1555242991
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.560 CONTRIBUTING VARIANT
Transcripts:
TBX3:ENST00000349155.7::
Pathogenicity Data:
Best Score: 0.560138
REMM: 0.560
Frequency Data:
No frequency data
DOWNSTREAM_GENE_VARIANT INS 12-114665427-C-CCCA [0/1] rs1555242989
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.560 CONTRIBUTING VARIANT
Transcripts:
TBX3:ENST00000349155.7::
Pathogenicity Data:
Best Score: 0.560138
REMM: 0.560
Frequency Data:
No frequency data
Other passed variants:
DOWNSTREAM_GENE_VARIANT SNV 12-114665424-G-C [1/1]
Variant score: 0.346
Transcripts:
TBX3:ENST00000349155.7::
Pathogenicity Data:
Best Score: 0.345943
REMM: 0.346
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT DEL 12-114688804-ACCACC-A [0/1] rs371749724
Variant score: 0.003
Transcripts:
TBX3:ENST00000349155.7::
Pathogenicity Data:
Best Score: 0.00252341
REMM: 0.003
Frequency Data:
No frequency data

CHRNG

Exomiser Score: 0.118 (p=2.5E-1)

Phenotype Score: 0.531

Variant Score: 0.626

Phenotype matches:
Phenotypic similarity 0.531 to Escobar syndrome associated with CHRNG.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0002557, Hypoplastic nipples
HP:0006625, Multifocal breast carcinoma - HP:0002557, Hypoplastic nipples
Proximity score 0.506 in interactome to DPAGT1 and phenotypic similarity 0.643 to Congenital disorder of glycosylation, type Ij associated with DPAGT1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Known diseases:
OMIM:253290 Multiple pterygium syndrome, lethal type - autosomal recessive
OMIM:265000 Escobar syndrome - autosomal recessive
ORPHA:2990 Autosomal recessive multiple pterygium syndrome - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.118 (p=2.5E-1)

Phenotype Score: 0.531

Variant Score: 0.626

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.531 to OMIM:265000 Escobar syndrome
Phenotypic similarity 0.474 to ORPHA:2990 Autosomal recessive multiple pterygium syndrome
Phenotypic similarity 0.434 to OMIM:253290 Multiple pterygium syndrome, lethal type
Variants contributing to score:
REGULATORY_REGION_VARIANT SNV 2-232512865-C-T [0/1] rs11687197
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.812 CONTRIBUTING VARIANT
Transcripts:
Pathogenicity Data:
Best Score: 0.902464
REMM: 0.902
Frequency Data:
UK10K: 0.5554%
gnomAD_G_AFR: 0.1107%
gnomAD_G_AMR: 0.2485%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.5233%
MISSENSE_VARIANT SNV 2-232545678-C-T [0/1] rs71421651
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:1, LB:2, B:4)
Variant score: 0.441 CONTRIBUTING VARIANT
Transcripts:
CHRNG:ENST00000651502.1:c.1516C>T:p.(Pro506Ser)
CHRNG:ENST00000408957.7:c.*2429G>A:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.9654%
gnomAD_E_AFR: 0.1075%
gnomAD_E_AMR: 0.2303%
gnomAD_E_NFE: 0.9218%
gnomAD_E_SAS: 1.0863%
gnomAD_G_AFR: 0.1467%
gnomAD_G_AMR: 0.4703%
gnomAD_G_NFE: 0.8614%
gnomAD_G_SAS: 0.9321%

PRKAG2

Exomiser Score: 0.118 (p=2.5E-1)

Phenotype Score: 0.504

Variant Score: 0.657

Phenotype matches:
Proximity score 0.504 in interactome to STK11 and phenotypic similarity 0.998 to Peutz-Jeghers syndrome associated with STK11.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.504 in interactome to STK11 and phenotypic similarity 0.306 to mouse mutant of STK11.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002825, abnormal notochord morphology
HP:0006625, Multifocal breast carcinoma - MP:0002825, abnormal notochord morphology
Known diseases:
OMIM:194200 Wolff-Parkinson-White syndrome - autosomal dominant
OMIM:261740 Glycogen storage disease of heart, lethal congenital - autosomal dominant
OMIM:600858 Cardiomyopathy, hypertrophic 6 - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.118 (p=2.5E-1)

Phenotype Score: 0.504

Variant Score: 0.657

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-151821039-C-CAGCCAGAAGGAAAGTAGAAGAGAGAGCCTCCAACCCCACAGACCTCAGTCCCGGCCAGAAGGAAAGTAGAAGAGAGAGCCTCCAACCCCACGGACCTCAGTCCCGGCCAGAAGGAAAGTAGAAGAGAGCCTCCAACCTCACGGACCTCAGTCCT [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.657 CONTRIBUTING VARIANT
Transcripts:
PRKAG2:ENST00000287878.9:c.115-34499_115-34498insAGGACTGAGGTCCGTGAGGTTGGAGGCTCTCTTCTACTTTCCTTCTGGCCGGGACTGAGGTCCGTGGGGTTGGAGGCTCTCTCTTCTACTTTCCTTCTGGCCGGGACTGAGGTCTGTGGGGTTGGAGGCTCTCTCTTCTACTTTCCTTCTGGCT:p.(=)
Pathogenicity Data:
Best Score: 0.65736
REMM: 0.657
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.106 (p=2.6E-1)

Phenotype Score: 0.252

Variant Score: 0.930

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-151688040-A-AAACCCC [1/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.930 CONTRIBUTING VARIANT
Transcripts:
PRKAG2:ENST00000287878.9:c.467-12404_467-12403insGGGGTT:p.(=)
Pathogenicity Data:
Best Score: 0.929724
REMM: 0.930
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151688041-G-C [1/1]
Variant score: 0.930
Transcripts:
PRKAG2:ENST00000287878.9:c.467-12404C>G:p.(=)
Pathogenicity Data:
Best Score: 0.929724
REMM: 0.930
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-151641244-CTTT-C [1/1] rs374667332
Variant score: 0.610
Transcripts:
PRKAG2:ENST00000287878.9:c.685-9109_685-9107del:p.(=)
Pathogenicity Data:
Best Score: 0.609886
REMM: 0.610
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-151842156-TGATGGTAGTGATGGTAGGTAGTGATGATGGTAGCAATGGTAGGTAGG-T [0/1] rs1323405906
Variant score: 0.581
Transcripts:
PRKAG2:ENST00000287878.9:c.114+34304_114+34350del:p.(=)
Pathogenicity Data:
Best Score: 0.581349
REMM: 0.581
Frequency Data:
gnomAD_G_NFE: 0.0077%
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-151827745-T-TAAAAA [0/1] rs55685618
Variant score: 0.502
Transcripts:
PRKAG2:ENST00000287878.9:c.115-41205_115-41204insTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.501897
REMM: 0.502
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-151623363-CA-C [0/1]
Variant score: 0.476
Transcripts:
PRKAG2:ENST00000287878.9:c.754+8705del:p.(=)
Pathogenicity Data:
Best Score: 0.476315
REMM: 0.476
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151738022-C-T [0/1] rs35594055
Variant score: 0.414
Transcripts:
PRKAG2:ENST00000287878.9:c.466+43130G>A:p.(=)
Pathogenicity Data:
Best Score: 0.414058
REMM: 0.414
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151738076-C-G [0/1]
Variant score: 0.406
Transcripts:
PRKAG2:ENST00000287878.9:c.466+43076G>C:p.(=)
Pathogenicity Data:
Best Score: 0.405837
REMM: 0.406
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151603486-C-T [0/1] rs368076011
Variant score: 0.402
Transcripts:
PRKAG2:ENST00000287878.9:c.755-8032G>A:p.(=)
Pathogenicity Data:
Best Score: 0.401652
REMM: 0.402
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-151673838-CT-C [1/1] rs57744338
Variant score: 0.367
Transcripts:
PRKAG2:ENST00000287878.9:c.684+1581del:p.(=)
Pathogenicity Data:
Best Score: 0.366698
REMM: 0.367
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151761581-C-G [0/1] rs117898078
Variant score: 0.357
Transcripts:
PRKAG2:ENST00000287878.9:c.466+19571G>C:p.(=)
Pathogenicity Data:
Best Score: 0.521086
REMM: 0.521
Frequency Data:
UK10K: 0.1455%
gnomAD_G_AFR: 0.0241%
gnomAD_G_AMR: 0.0589%
gnomAD_G_NFE: 0.1661%
gnomAD_G_SAS: 1.2033%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-151603233-ACG-A [0/1] rs1231224076
Variant score: 0.311
Transcripts:
PRKAG2:ENST00000287878.9:c.755-7781_755-7780del:p.(=)
Pathogenicity Data:
Best Score: 0.310859
REMM: 0.311
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151738036-C-A [1/1]
Variant score: 0.275
Transcripts:
PRKAG2:ENST00000287878.9:c.466+43116G>T:p.(=)
Pathogenicity Data:
Best Score: 0.275058
REMM: 0.275
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151738044-C-A [0/1]
Variant score: 0.270
Transcripts:
PRKAG2:ENST00000287878.9:c.466+43108G>T:p.(=)
Pathogenicity Data:
Best Score: 0.270422
REMM: 0.270
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-151874411-GATGTAT-G [1/1] rs1175860064
Variant score: 0.269
Transcripts:
PRKAG2:ENST00000287878.9:c.114+2090_114+2095del:p.(=)
Pathogenicity Data:
Best Score: 0.271729
REMM: 0.272
Frequency Data:
gnomAD_G_AMR: 0.0727%
gnomAD_G_NFE: 0.0027%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151603430-A-G [1/1] rs113796515
Variant score: 0.269
Transcripts:
PRKAG2:ENST00000287878.9:c.755-7976T>C:p.(=)
Pathogenicity Data:
Best Score: 0.268846
REMM: 0.269
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151855254-C-T [0/1] rs376851564
Variant score: 0.268
Transcripts:
PRKAG2:ENST00000287878.9:c.114+21253G>A:p.(=)
Pathogenicity Data:
Best Score: 0.273045
REMM: 0.273
Frequency Data:
gnomAD_G_AFR: 0.0439%
gnomAD_G_AMR: 0.1003%
gnomAD_G_NFE: 0.1374%
gnomAD_G_SAS: 0.0662%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151855061-A-G [0/1] rs201795227
Variant score: 0.236
Transcripts:
PRKAG2:ENST00000287878.9:c.114+21446T>C:p.(=)
Pathogenicity Data:
Best Score: 0.23559
REMM: 0.236
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-151874264-GTATATGTATATGATA-G [0/1] rs1191731893
Variant score: 0.227
Transcripts:
PRKAG2:ENST00000287878.9:c.114+2228_114+2242del:p.(=)
Pathogenicity Data:
Best Score: 0.370417
REMM: 0.370
Frequency Data:
gnomAD_G_AFR: 1.3484%
gnomAD_G_AMR: 1.1452%
gnomAD_G_EAS: 0.2250%
gnomAD_G_NFE: 1.2342%
gnomAD_G_SAS: 0.8630%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151855415-T-C [1/1] rs111163523
Variant score: 0.195
Transcripts:
PRKAG2:ENST00000287878.9:c.114+21092A>G:p.(=)
Pathogenicity Data:
Best Score: 0.194677
REMM: 0.195
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151855109-A-G [0/1]
Variant score: 0.174
Transcripts:
PRKAG2:ENST00000287878.9:c.114+21398T>C:p.(=)
Pathogenicity Data:
Best Score: 0.173702
REMM: 0.174
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151855062-T-C [1/1] rs200332217
Variant score: 0.172
Transcripts:
PRKAG2:ENST00000287878.9:c.114+21445A>G:p.(=)
Pathogenicity Data:
Best Score: 0.171988
REMM: 0.172
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151830790-G-T [0/1] rs116346767
Variant score: 0.172
Transcripts:
PRKAG2:ENST00000287878.9:c.115-44249C>A:p.(=)
Pathogenicity Data:
Best Score: 0.171941
REMM: 0.172
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-151773075-GAGGGAGGGAGGGAGGGAGGGAAGGGA-G [0/1]
Variant score: 0.166
Transcripts:
PRKAG2:ENST00000287878.9:c.466+8051_466+8076del:p.(=)
Pathogenicity Data:
Best Score: 0.166015
REMM: 0.166
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-151773056-AGGGAGGGAGGGAGG-A [0/1]
Variant score: 0.157
Transcripts:
PRKAG2:ENST00000287878.9:c.466+8082_466+8095del:p.(=)
Pathogenicity Data:
Best Score: 0.157313
REMM: 0.157
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151738082-C-T [0/1]
Variant score: 0.091
Transcripts:
PRKAG2:ENST00000287878.9:c.466+43070G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0914433
REMM: 0.091
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151738085-C-A [0/1]
Variant score: 0.056
Transcripts:
PRKAG2:ENST00000287878.9:c.466+43067G>T:p.(=)
Pathogenicity Data:
Best Score: 0.0562639
REMM: 0.056
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151816184-A-T [0/1] rs1189502014
Variant score: 0.043
Transcripts:
PRKAG2:ENST00000287878.9:c.115-29643T>A:p.(=)
Pathogenicity Data:
Best Score: 0.0430044
REMM: 0.043
Frequency Data:
gnomAD_G_AMR: 0.0065%
gnomAD_G_NFE: 0.0029%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151855378-G-A [0/1] rs201666080
Variant score: 0.028
Transcripts:
PRKAG2:ENST00000287878.9:c.114+21129C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0284422
REMM: 0.028
Frequency Data:
gnomAD_G_AFR: 0.2143%
gnomAD_G_AMR: 0.1587%
gnomAD_G_NFE: 0.1894%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151738033-C-T [1/1] rs7781561
Variant score: 0.021
Transcripts:
PRKAG2:ENST00000287878.9:c.466+43119G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0214258
REMM: 0.021
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-151671171-CA-C [1/1]
Variant score: 0.019
Transcripts:
PRKAG2:ENST00000287878.9:c.684+4248del:p.(=)
Pathogenicity Data:
Best Score: 0.0189353
REMM: 0.019
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151819521-C-T [0/1] rs142950780
Variant score: 0.015
Transcripts:
PRKAG2:ENST00000287878.9:c.115-32980G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0237984
REMM: 0.024
Frequency Data:
gnomAD_G_AFR: 0.2719%
gnomAD_G_AMR: 0.9809%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.2938%
gnomAD_G_SAS: 0.2905%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151794611-C-A [0/1]
Variant score: 0.014
Transcripts:
PRKAG2:ENST00000287878.9:c.115-8070G>T:p.(=)
Pathogenicity Data:
Best Score: 0.0137587
REMM: 0.014
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151842448-G-A [0/1] rs868494149
Variant score: 0.012
Transcripts:
PRKAG2:ENST00000287878.9:c.114+34059C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0126464
REMM: 0.013
Frequency Data:
gnomAD_G_AFR: 0.0869%
gnomAD_G_AMR: 0.0090%
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-151848512-C-CTTTT [0/1] rs1158559692
Variant score: 0.009
Transcripts:
PRKAG2:ENST00000287878.9:c.114+27994_114+27995insAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.00867976
REMM: 0.009
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151782365-G-A [0|1]
Variant score: 0.007
Transcripts:
PRKAG2:ENST00000287878.9:c.187-934C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00749524
REMM: 0.007
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151738027-G-C [0/1] rs7781815
Variant score: 0.002
Transcripts:
PRKAG2:ENST00000287878.9:c.466+43125C>G:p.(=)
Pathogenicity Data:
Best Score: 0.00234286
REMM: 0.002
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151824469-C-T [0/1] rs139958503
Variant score: 0.002
Transcripts:
PRKAG2:ENST00000287878.9:c.115-37928G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00422222
REMM: 0.004
Frequency Data:
UK10K: 1.6662%
gnomAD_G_AFR: 0.2792%
gnomAD_G_AMR: 0.9486%
gnomAD_G_NFE: 1.3450%
gnomAD_G_SAS: 0.3109%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151849872-A-G [0/1] rs1008671239
Variant score: 0.000
Transcripts:
PRKAG2:ENST00000287878.9:c.114+26635T>C:p.(=)
Pathogenicity Data:
Best Score: 5.0E-4
REMM: 0.001
Frequency Data:
gnomAD_G_NFE: 0.0044%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151860084-C-T [0/1] rs998914376
Variant score: 0.000
Transcripts:
PRKAG2:ENST00000287878.9:c.114+16423G>A:p.(=)
Pathogenicity Data:
Best Score: 1.66667E-4
REMM: 0.000
Frequency Data:
gnomAD_G_NFE: 0.0029%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-151846664-G-A [0/1] rs866847730
Variant score: 0.000
Transcripts:
PRKAG2:ENST00000287878.9:c.114+29843C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_NFE: 0.0191%

PTEN

Exomiser Score: 0.116 (p=2.5E-1)

Phenotype Score: 0.998

Variant Score: 0.096

Phenotype matches:
Phenotypic similarity 0.998 to Hereditary breast and/or ovarian cancer syndrome associated with PTEN.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Phenotypic similarity 0.303 to zebrafish mutant involving PTEN.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0000122, notochord undulate, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0000122, notochord undulate, abnormal
Proximity score 0.503 in interactome to STK11 and phenotypic similarity 0.998 to Peutz-Jeghers syndrome associated with STK11.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.503 in interactome to STK11 and phenotypic similarity 0.306 to mouse mutant of STK11.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002825, abnormal notochord morphology
HP:0006625, Multifocal breast carcinoma - MP:0002825, abnormal notochord morphology
Known diseases:
OMIM:158350 Cowden syndrome 1 - autosomal dominant
OMIM:176807 Prostate cancer, somatic - autosomal dominant
OMIM:605309 Macrocephaly/autism syndrome - autosomal dominant
OMIM:607174 Meningioma (susceptibility)
OMIM:613028 Glioma susceptibility 2 (susceptibility)
ORPHA:101070 Bilateral frontoparietal polymicrogyria - unknown
ORPHA:109 Bannayan-Riley-Ruvalcaba syndrome - autosomal dominant
ORPHA:145 Hereditary breast and/or ovarian cancer syndrome - autosomal dominant
ORPHA:201 Cowden syndrome - autosomal dominant
ORPHA:210548 Macrocephaly-intellectual disability-autism syndrome - autosomal dominant
ORPHA:2969 Proteus-like syndrome - autosomal dominant
ORPHA:397596 Activated PI3K-delta syndrome - autosomal dominant
ORPHA:65285 Lhermitte-Duclos disease - autosomal dominant
ORPHA:744 Proteus syndrome - unknown
ORPHA:79076 Juvenile polyposis of infancy (CNV)
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.116 (p=2.5E-1)

Phenotype Score: 0.998

Variant Score: 0.096

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.998 to ORPHA:145 Hereditary breast and/or ovarian cancer syndrome
Phenotypic similarity 0.910 to OMIM:158350 Cowden syndrome 1
Phenotypic similarity 0.904 to ORPHA:201 Cowden syndrome
Phenotypic similarity 0.887 to ORPHA:109 Bannayan-Riley-Ruvalcaba syndrome
Phenotypic similarity 0.876 to ORPHA:65285 Lhermitte-Duclos disease
Phenotypic similarity 0.312 to ORPHA:79076 Juvenile polyposis of infancy
Variants contributing to score:
INTERGENIC_VARIANT DEL 10-87985763-CAAAAAAAAAAA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting, PP4]
Variant score: 0.096 CONTRIBUTING VARIANT
Transcripts:
PTEN:ENST00000371953.8::
Pathogenicity Data:
Best Score: 0.0962603
REMM: 0.096
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.004 (p=5.7E-1)

Phenotype Score: 0.252

Variant Score: 0.566

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 10-87939294-GTTTT-G [1/1] rs71022513
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.566 CONTRIBUTING VARIANT
Transcripts:
PTEN:ENST00000371953.8:c.492+6044_492+6047del:p.(=)
Pathogenicity Data:
Best Score: 0.566168
REMM: 0.566
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-87918011-C-T [0/1] rs187607407
Variant score: 0.723
Transcripts:
PTEN:ENST00000371953.8:c.165-7502C>T:p.(=)
Pathogenicity Data:
Best Score: 0.748046
REMM: 0.748
Frequency Data:
UK10K: 0.2248%
gnomAD_G_AFR: 0.0440%
gnomAD_G_AMR: 0.1651%
gnomAD_G_NFE: 0.1868%
gnomAD_G_SAS: 0.0622%
INTERGENIC_VARIANT DEL 10-87985763-CAAAA-C [0/1]
Variant score: 0.096
Transcripts:
PTEN:ENST00000371953.8::
Pathogenicity Data:
Best Score: 0.0962603
REMM: 0.096
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 10-87914129-G-GT [0/1] rs771214496
Variant score: 0.074
Transcripts:
PTEN:ENST00000371953.8:c.165-11384_165-11383insT:p.(=)
Pathogenicity Data:
Best Score: 0.497723
REMM: 0.498
Frequency Data:
gnomAD_G_AFR: 1.9381%
gnomAD_G_AMR: 1.1316%
gnomAD_G_EAS: 1.3131%
gnomAD_G_NFE: 1.9875%
gnomAD_G_SAS: 1.1155%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-87904289-C-T [0/1] rs374996638
Variant score: 0.054
Transcripts:
PTEN:ENST00000371953.8:c.164+10180C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0538837
REMM: 0.054
Frequency Data:
gnomAD_G_AFR: 0.0120%
gnomAD_G_AMR: 0.0262%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.0221%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-87907534-C-T [0/1] rs143199046
Variant score: 0.014
Transcripts:
PTEN:ENST00000371953.8:c.164+13425C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0141635
REMM: 0.014
Frequency Data:
UK10K: 0.1455%
gnomAD_G_AFR: 0.0190%
gnomAD_G_AMR: 0.0210%
gnomAD_G_NFE: 0.1018%

NUP153

Exomiser Score: 0.113 (p=2.5E-1)

Phenotype Score: 0.501

Variant Score: 0.655

Phenotype matches:
Proximity score 0.501 in interactome to NUP107 and phenotypic similarity 0.676 to 46,XX gonadal dysgenesis associated with NUP107.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
HP:0006625, Multifocal breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
Proximity score 0.501 in interactome to NUP107 and phenotypic similarity 0.225 to fish mutant of NUP107.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0016453, pharyngeal arch has fewer parts of type chondroblast nuclear pore chondroblast, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0016453, pharyngeal arch has fewer parts of type chondroblast nuclear pore chondroblast, abnormal
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.113 (p=2.5E-1)

Phenotype Score: 0.501

Variant Score: 0.655

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-17665052-C-CAAAAAAAAAAAAAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.655 CONTRIBUTING VARIANT
Transcripts:
NUP153:ENST00000262077.3:c.1215+186_1215+187insTTTTTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.655187
REMM: 0.655
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.113 (p=2.5E-1)

Phenotype Score: 0.501

Variant Score: 0.655

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-17665052-C-CAAAAAAAAAAAAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.655 CONTRIBUTING VARIANT
Transcripts:
NUP153:ENST00000262077.3:c.1215+186_1215+187insTTTTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.655187
REMM: 0.655
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-17665052-C-CAAAAAAAAAAAAAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.655 CONTRIBUTING VARIANT
Transcripts:
NUP153:ENST00000262077.3:c.1215+186_1215+187insTTTTTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.655187
REMM: 0.655
Frequency Data:
No frequency data
Other passed variants:
MISSENSE_VARIANT SNV 6-17649242-G-A [0/1] rs143083233
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.592
Transcripts:
NUP153:ENST00000262077.3:c.1454C>T:p.(Pro485Leu)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 0.0060%
gnomAD_E_AMR: 0.0962%
gnomAD_E_NFE: 0.0359%
gnomAD_E_SAS: 0.0151%
gnomAD_G_AFR: 0.0096%
gnomAD_G_AMR: 0.0654%
gnomAD_G_NFE: 0.0426%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-17670095-CA-C [1/1] rs71002244
Variant score: 0.488
Transcripts:
NUP153:ENST00000262077.3:c.853-550del:p.(=)
Pathogenicity Data:
Best Score: 0.488296
REMM: 0.488
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-17702599-C-G [0/1] rs140049385
Variant score: 0.375
Transcripts:
NUP153:ENST00000262077.3:c.111+3678G>C:p.(=)
Pathogenicity Data:
Best Score: 0.782735
REMM: 0.783
Frequency Data:
UK10K: 1.1108%
gnomAD_G_AFR: 0.1617%
gnomAD_G_AMR: 0.9180%
gnomAD_G_NFE: 1.4787%
gnomAD_G_SAS: 1.5781%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-17697731-A-C [0/1] rs142896907
Variant score: 0.211
Transcripts:
NUP153:ENST00000262077.3:c.111+8546T>G:p.(=)
Pathogenicity Data:
Best Score: 0.439626
REMM: 0.440
Frequency Data:
UK10K: 1.1108%
gnomAD_G_AFR: 0.1676%
gnomAD_G_AMR: 0.9031%
gnomAD_G_NFE: 1.4796%
gnomAD_G_SAS: 1.5783%
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-17686689-G-GA [0/1] rs547444412
Variant score: 0.111
Transcripts:
NUP153:ENST00000262077.3:c.334+1706_334+1707insT:p.(=)
Pathogenicity Data:
Best Score: 0.240138
REMM: 0.240
Frequency Data:
gnomAD_G_AFR: 0.1707%
gnomAD_G_AMR: 1.0581%
gnomAD_G_NFE: 1.5336%
gnomAD_G_SAS: 1.6024%
DOWNSTREAM_GENE_VARIANT SNV 6-17614639-G-C [1/1] rs9371005
Variant score: 0.006
Transcripts:
NUP153:ENST00000262077.3::
Pathogenicity Data:
Best Score: 0.0064
REMM: 0.006
Frequency Data:
No frequency data
DOWNSTREAM_GENE_VARIANT SNV 6-17612880-C-T [0/1] rs116154316
Variant score: 0.000
Transcripts:
NUP153:ENST00000262077.3::
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 1.4017%
gnomAD_G_AFR: 0.3105%
gnomAD_G_AMR: 0.3594%
gnomAD_G_NFE: 1.6889%
gnomAD_G_SAS: 0.2692%

GATA3

Exomiser Score: 0.113 (p=2.5E-1)

Phenotype Score: 0.510

Variant Score: 0.645

Phenotype matches:
Phenotypic similarity 0.349 to mouse mutant involving GATA3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002116, abnormal craniofacial bone morphology
HP:0006625, Multifocal breast carcinoma - MP:0002116, abnormal craniofacial bone morphology
Phenotypic similarity 0.281 to zebrafish mutant involving GATA3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0010443, neurocranium lacks all parts of type neurocranial trabecula, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0010443, neurocranium lacks all parts of type neurocranial trabecula, abnormal
Proximity score 0.510 in interactome to ZFPM2 and phenotypic similarity 0.614 to 46,XY partial gonadal dysgenesis associated with ZFPM2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Known diseases:
OMIM:146255 Hypoparathyroidism, sensorineural deafness, and renal dysplasia - autosomal dominant
ORPHA:2237 Hypoparathyroidism-sensorineural deafness-renal disease syndrome - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.113 (p=2.5E-1)

Phenotype Score: 0.510

Variant Score: 0.645

No phenotype matches to diseases with this MOI.
Variants contributing to score:
INTERGENIC_VARIANT INS 10-8087040-C-CTTTTTTTTTTTT [0/1] rs10661114
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.645 CONTRIBUTING VARIANT
Transcripts:
GATA3:ENST00000379328.9::
Pathogenicity Data:
Best Score: 0.645238
REMM: 0.645
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.008 (p=4.9E-1)

Phenotype Score: 0.255

Variant Score: 0.637

No phenotype matches to diseases with this MOI.
Variants contributing to score:
INTERGENIC_VARIANT INS 10-8087040-C-CTTTTTTTTTTTT [0/1] rs10661114
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.645 CONTRIBUTING VARIANT
Transcripts:
GATA3:ENST00000379328.9::
Pathogenicity Data:
Best Score: 0.645238
REMM: 0.645
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-8066664-G-A [0/1] rs9664358
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.629 CONTRIBUTING VARIANT
Transcripts:
GATA3:ENST00000379328.9:c.924+2526G>A:p.(=)
Pathogenicity Data:
Best Score: 0.794661
REMM: 0.795
Frequency Data:
UK10K: 0.1455%
gnomAD_G_AFR: 0.0169%
gnomAD_G_AMR: 0.0849%
gnomAD_G_NFE: 0.1485%
gnomAD_G_SAS: 0.9328%
Other passed variants:
INTERGENIC_VARIANT DEL 10-8086168-CAA-C [0/1]
Variant score: 0.380
Transcripts:
GATA3:ENST00000379328.9::
Pathogenicity Data:
Best Score: 0.380428
REMM: 0.380
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 10-8073144-CA-C [0/1]
Variant score: 0.328
Transcripts:
GATA3:ENST00000379328.9:c.1051-594del:p.(=)
Pathogenicity Data:
Best Score: 0.328278
REMM: 0.328
Frequency Data:
No frequency data
INTERGENIC_VARIANT INS 10-8086168-C-CAAAAAAAA [0/1]
Variant score: 0.322
Transcripts:
GATA3:ENST00000379328.9::
Pathogenicity Data:
Best Score: 0.32161
REMM: 0.322
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 10-8035133-C-T [0/1]
Variant score: 0.292
Transcripts:
GATA3:ENST00000379328.9::
Pathogenicity Data:
Best Score: 0.292211
REMM: 0.292
Frequency Data:
No frequency data
REGULATORY_REGION_VARIANT INS 10-9097560-T-TAAAAAAA [0/1]
Variant score: 0.196
Transcripts:
GATA3:ENST00000379328.9::
Pathogenicity Data:
Best Score: 0.195578
REMM: 0.196
Frequency Data:
No frequency data
REGULATORY_REGION_VARIANT INS 10-9097560-T-TAAAAAAAA [0/1] rs55988366
Variant score: 0.164
Transcripts:
GATA3:ENST00000379328.9::
Pathogenicity Data:
Best Score: 0.195578
REMM: 0.196
Frequency Data:
gnomAD_G_AFR: 0.4997%
gnomAD_G_AMR: 0.3000%
gnomAD_G_EAS: 0.6173%
gnomAD_G_NFE: 0.7926%
INTERGENIC_VARIANT INS 10-8092486-G-GA [0/1] rs1429638971
Variant score: 0.024
Transcripts:
GATA3:ENST00000379328.9::
Pathogenicity Data:
Best Score: 0.023881
REMM: 0.024
Frequency Data:
gnomAD_G_AFR: 0.0024%
gnomAD_G_NFE: 0.0177%
gnomAD_G_SAS: 0.0208%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-8069667-C-G [0/1]
Variant score: 0.000
Transcripts:
GATA3:ENST00000379328.9:c.1050+69C>G:p.(=)
Pathogenicity Data:
Best Score: 2.77778E-4
REMM: 0.000
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 10-8080432-G-A [0/1] rs112806755
Variant score: 0.000
Transcripts:
GATA3:ENST00000379328.9::
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.2645%
gnomAD_G_AFR: 0.1159%
gnomAD_G_AMR: 0.6884%
gnomAD_G_EAS: 0.0387%
gnomAD_G_NFE: 0.5325%
gnomAD_G_SAS: 1.8919%

LAMB2

Exomiser Score: 0.111 (p=2.5E-1)

Phenotype Score: 0.502

Variant Score: 0.653

Phenotype matches:
Phenotypic similarity 0.368 to Synaptic congenital myasthenic syndromes associated with LAMB2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003691, Scapular winging
HP:0006625, Multifocal breast carcinoma - HP:0003691, Scapular winging
Phenotypic similarity 0.323 to zebrafish mutant involving LAMB2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0000624, notochord morphology, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0000624, notochord morphology, abnormal
Proximity score 0.502 in interactome to ITGA3 and phenotypic similarity 0.603 to Epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome associated with ITGA3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Known diseases:
OMIM:609049 Pierson syndrome - autosomal recessive
OMIM:614199 Nephrotic syndrome, type 5, with or without ocular abnormalities - autosomal recessive
ORPHA:98915 Synaptic congenital myasthenic syndromes - unknown
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.111 (p=2.5E-1)

Phenotype Score: 0.502

Variant Score: 0.653

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-49122678-T-C [0/1] rs369814137
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.902 CONTRIBUTING VARIANT
Transcripts:
LAMB2:ENST00000305544.9:c.4573+26A>G:p.(=)
Pathogenicity Data:
Best Score: 0.913398
REMM: 0.913
Frequency Data:
gnomAD_E_NFE: 0.0020%
gnomAD_E_SAS: 0.0885%
gnomAD_G_AFR: 0.0024%
gnomAD_G_NFE: 0.0029%
gnomAD_G_SAS: 0.0621%
UPSTREAM_GENE_VARIANT INS 3-49134184-A-ATTTTTTTTTTT [0/1] rs1190013970
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.403 CONTRIBUTING VARIANT
Transcripts:
LAMB2:ENST00000305544.9::
Pathogenicity Data:
Best Score: 0.403236
REMM: 0.403
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.083 (p=2.8E-1)

Phenotype Score: 0.251

Variant Score: 0.902

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-49122678-T-C [0/1] rs369814137
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.902 CONTRIBUTING VARIANT
Transcripts:
LAMB2:ENST00000305544.9:c.4573+26A>G:p.(=)
Pathogenicity Data:
Best Score: 0.913398
REMM: 0.913
Frequency Data:
gnomAD_E_NFE: 0.0020%
gnomAD_E_SAS: 0.0885%
gnomAD_G_AFR: 0.0024%
gnomAD_G_NFE: 0.0029%
gnomAD_G_SAS: 0.0621%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-49131345-G-A [0/1] rs369592107
Variant score: 0.130
Transcripts:
LAMB2:ENST00000305544.9:c.712+34C>T:p.(=)
Pathogenicity Data:
Best Score: 0.147075
REMM: 0.147
Frequency Data:
UK10K: 0.0793%
gnomAD_E_AFR: 0.0060%
gnomAD_E_AMR: 0.0784%
gnomAD_E_EAS: 0.0025%
gnomAD_E_NFE: 0.0538%
gnomAD_E_SAS: 0.6328%
gnomAD_G_AFR: 0.0096%
gnomAD_G_AMR: 0.1766%
gnomAD_G_NFE: 0.0441%
gnomAD_G_SAS: 0.4137%
SYNONYMOUS_VARIANT SNV 3-49126004-G-A [0/1] rs147076626
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:1, LB:3, B:2)
Variant score: 0.086
Transcripts:
LAMB2:ENST00000305544.9:c.2307C>T:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.4761%
gnomAD_E_AFR: 0.0538%
gnomAD_E_AMR: 0.1789%
gnomAD_E_NFE: 0.3835%
gnomAD_E_SAS: 0.7118%
gnomAD_G_AFR: 0.0914%
gnomAD_G_AMR: 0.3202%
gnomAD_G_NFE: 0.3704%
gnomAD_G_SAS: 0.4975%

UBE3A

Exomiser Score: 0.110 (p=2.6E-1)

Phenotype Score: 0.502

Variant Score: 0.651

Phenotype matches:
Phenotypic similarity 0.321 to mouse mutant involving UBE3A.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0010124, decreased bone mineral content
HP:0006625, Multifocal breast carcinoma - MP:0010124, decreased bone mineral content
Proximity score 0.502 in interactome to TERT and phenotypic similarity 0.950 to Familial melanoma associated with TERT.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0100013, Neoplasm of the breast
HP:0006625, Multifocal breast carcinoma - HP:0100013, Neoplasm of the breast
Proximity score 0.502 in interactome to TERT and phenotypic similarity 0.357 to mouse mutant of TERT.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0003345, decreased rib number
HP:0006625, Multifocal breast carcinoma - MP:0003345, decreased rib number
Known diseases:
OMIM:105830 Angelman syndrome - autosomal dominant
ORPHA:238446 15q11q13 microduplication syndrome (CNV)
ORPHA:411511 Angelman syndrome due to a point mutation - autosomal dominant
ORPHA:98795 Angelman syndrome due to paternal uniparental disomy of chromosome 15 (CNV)
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.110 (p=2.6E-1)

Phenotype Score: 0.502

Variant Score: 0.651

No phenotype matches to diseases with this MOI.
Variants contributing to score:
FIVE_PRIME_UTR_INTRON_VARIANT DEL 15-25427602-CAAA-C [0/1] rs751567252
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.651 CONTRIBUTING VARIANT
Transcripts:
UBE3A:ENST00000648336.2:c.-165+10884_-165+10886del:p.(=)
Pathogenicity Data:
Best Score: 0.650681
REMM: 0.651
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.007 (p=5.1E-1)

Phenotype Score: 0.251

Variant Score: 0.625

No phenotype matches to diseases with this MOI.
Variants contributing to score:
FIVE_PRIME_UTR_INTRON_VARIANT DEL 15-25427602-CAAA-C [0/1] rs751567252
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.651 CONTRIBUTING VARIANT
Transcripts:
UBE3A:ENST00000648336.2:c.-165+10884_-165+10886del:p.(=)
Pathogenicity Data:
Best Score: 0.650681
REMM: 0.651
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT INS 15-25427602-C-CA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.599 CONTRIBUTING VARIANT
Transcripts:
UBE3A:ENST00000648336.2:c.-165+10886_-165+10887insT:p.(=)
Pathogenicity Data:
Best Score: 0.599336
REMM: 0.599
Frequency Data:
No frequency data
Other passed variants:
FIVE_PRIME_UTR_INTRON_VARIANT DEL 15-25434969-TACACACACACAC-T [0/1] rs55856025
Variant score: 0.594
Transcripts:
UBE3A:ENST00000648336.2:c.-165+3508_-165+3519del:p.(=)
Pathogenicity Data:
Best Score: 0.594411
REMM: 0.594
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 15-25357902-CTTT-C [0/1] rs35596421
Variant score: 0.535
Transcripts:
UBE3A:ENST00000648336.2:c.1754-1009_1754-1007del:p.(=)
Pathogenicity Data:
Best Score: 0.534594
REMM: 0.535
Frequency Data:
No frequency data
THREE_PRIME_UTR_EXON_VARIANT INS 15-25336473-C-CAA [0|1] rs756191173
Variant score: 0.494
Transcripts:
UBE3A:ENST00000648336.2:c.*2663_*2664insTT:p.(=)
Pathogenicity Data:
Best Score: 0.494742
REMM: 0.495
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AMR: 0.0065%
gnomAD_G_NFE: 0.0074%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 15-25398167-CA-C [0/1]
Variant score: 0.354
Transcripts:
UBE3A:ENST00000648336.2:c.62+7293del:p.(=)
Pathogenicity Data:
Best Score: 0.354113
REMM: 0.354
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT INS 15-25430266-C-CAT [1/1]
Variant score: 0.310
Transcripts:
UBE3A:ENST00000648336.2:c.-165+8222_-165+8223insAT:p.(=)
Pathogenicity Data:
Best Score: 0.310096
REMM: 0.310
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 15-25403211-C-T [0/1] rs145645787
Variant score: 0.004
Transcripts:
UBE3A:ENST00000648336.2:c.62+2250G>A:p.(=)
Pathogenicity Data:
Best Score: 0.00439802
REMM: 0.004
Frequency Data:
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0327%
gnomAD_G_NFE: 0.0176%
gnomAD_G_SAS: 0.0207%

HS3ST6

Exomiser Score: 0.108 (p=2.6E-1)

Phenotype Score: 0.506

Variant Score: 0.645

Phenotype matches:
Proximity score 0.506 in interactome to HS6ST1 and phenotypic similarity 0.620 to Kallmann syndrome associated with HS6ST1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003187, Breast hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0003187, Breast hypoplasia
Proximity score 0.506 in interactome to HS6ST1 and phenotypic similarity 0.318 to mouse mutant of HS6ST1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002113, abnormal skeleton development
HP:0006625, Multifocal breast carcinoma - MP:0002113, abnormal skeleton development
Known diseases:
OMIM:619367 ?Angioedema, hereditary, 8 (unconfirmed)
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.108 (p=2.6E-1)

Phenotype Score: 0.506

Variant Score: 0.645

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 16-1916148-C-CCCCACGTGGCCACGGCCCCTCGGAGAGCACAAGGACACCCGCAGTCGGGAAGCTCAGCGGG [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.645 CONTRIBUTING VARIANT
Transcripts:
HS3ST6:ENST00000454677.3:c.413+1762_413+1763insCCCGCTGAGCTTCCCGACTGCGGGTGTCCTTGTGCTCTCCGAGGGGCCGTGGCCACGTGGG:p.(=)
Pathogenicity Data:
Best Score: 0.644612
REMM: 0.645
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.001 (p=7.7E-1)

Phenotype Score: 0.253

Variant Score: 0.357

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 16-1916148-C-CCCCACGTGGCCACGGCCCCTCGGAGAGCACAAGGACACCCGCAGTCGGGAAGCTCAGCGGG [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.645 CONTRIBUTING VARIANT
Transcripts:
HS3ST6:ENST00000454677.3:c.413+1762_413+1763insCCCGCTGAGCTTCCCGACTGCGGGTGTCCTTGTGCTCTCCGAGGGGCCGTGGCCACGTGGG:p.(=)
Pathogenicity Data:
Best Score: 0.644612
REMM: 0.645
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT SNV 16-1919440-G-A [0/1] rs1019015404
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.070 CONTRIBUTING VARIANT
Transcripts:
HS3ST6:ENST00000454677.3::
Pathogenicity Data:
Best Score: 0.0702964
REMM: 0.070
Frequency Data:
gnomAD_G_AMR: 0.0327%
gnomAD_G_NFE: 0.0015%

KIF9

Exomiser Score: 0.105 (p=2.6E-1)

Phenotype Score: 0.505

Variant Score: 0.642

Phenotype matches:
Proximity score 0.505 in interactome to SH3PXD2B and phenotypic similarity 0.614 to Frank-Ter Haar syndrome associated with SH3PXD2B.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Proximity score 0.505 in interactome to SH3PXD2B and phenotypic similarity 0.346 to mouse mutant of SH3PXD2B.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000160, kyphosis
HP:0006625, Multifocal breast carcinoma - MP:0000160, kyphosis
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.105 (p=2.6E-1)

Phenotype Score: 0.505

Variant Score: 0.642

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-47239743-A-T [0/1] rs146414099
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.689 CONTRIBUTING VARIANT
Transcripts:
KIF9:ENST00000684063.1:c.1924+1058T>A:p.(=)
Pathogenicity Data:
Best Score: 0.794208
REMM: 0.794
Frequency Data:
UK10K: 0.6348%
gnomAD_E_AFR: 0.1381%
gnomAD_E_AMR: 0.4557%
gnomAD_E_NFE: 0.5332%
gnomAD_E_SAS: 0.0529%
gnomAD_G_AFR: 0.0722%
gnomAD_G_AMR: 0.6803%
gnomAD_G_NFE: 0.6101%
gnomAD_G_SAS: 0.0623%
MISSENSE_VARIANT SNV 3-47265736-A-T [0/1] rs138701088
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.595 CONTRIBUTING VARIANT
Transcripts:
KIF9:ENST00000684063.1:c.910T>A:p.(Ser304Thr)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.0132%
gnomAD_E_AFR: 0.0090%
gnomAD_E_AMR: 0.0581%
gnomAD_E_NFE: 0.0348%
gnomAD_G_AFR: 0.0097%
gnomAD_G_AMR: 0.0262%
gnomAD_G_NFE: 0.0559%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.071 (p=2.9E-1)

Phenotype Score: 0.505

Variant Score: 0.595

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 3-47265736-A-T [0/1] rs138701088
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.595 CONTRIBUTING VARIANT
Transcripts:
KIF9:ENST00000684063.1:c.910T>A:p.(Ser304Thr)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.0132%
gnomAD_E_AFR: 0.0090%
gnomAD_E_AMR: 0.0581%
gnomAD_E_NFE: 0.0348%
gnomAD_G_AFR: 0.0097%
gnomAD_G_AMR: 0.0262%
gnomAD_G_NFE: 0.0559%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT INS 3-47269768-A-ATT [0/1] rs36108313
Variant score: 0.261
Transcripts:
KIF9:ENST00000684063.1:c.591+1468_591+1469insAA:p.(=)
Pathogenicity Data:
Best Score: 0.327797
REMM: 0.328
Frequency Data:
gnomAD_G_AFR: 0.7703%
gnomAD_G_AMR: 0.5240%
gnomAD_G_EAS: 0.1054%
gnomAD_G_NFE: 0.9174%
gnomAD_G_SAS: 0.6133%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-47250403-C-G [0/1] rs76760534
Variant score: 0.097
Transcripts:
KIF9:ENST00000684063.1:c.1060-2317G>C:p.(=)
Pathogenicity Data:
Best Score: 0.667955
REMM: 0.668
Frequency Data:
UK10K: 1.3621%
gnomAD_E_AFR: 0.5319%
gnomAD_E_AMR: 0.6949%
gnomAD_E_NFE: 1.3821%
gnomAD_E_SAS: 1.7927%
gnomAD_G_AFR: 0.5150%
gnomAD_G_AMR: 0.8301%
gnomAD_G_NFE: 1.6203%
gnomAD_G_SAS: 1.9900%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-47269052-G-A [0/1] rs914968599
Variant score: 0.001
Transcripts:
KIF9:ENST00000684063.1:c.592-1789C>T:p.(=)
Pathogenicity Data:
Best Score: 0.001
REMM: 0.001
Frequency Data:
gnomAD_G_AFR: 0.0024%
gnomAD_G_NFE: 0.0132%

FGFR4

Exomiser Score: 0.104 (p=2.6E-1)

Phenotype Score: 0.504

Variant Score: 0.642

Phenotype matches:
Proximity score 0.504 in interactome to FGF17 and phenotypic similarity 0.620 to Kallmann syndrome associated with FGF17.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003187, Breast hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0003187, Breast hypoplasia
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.104 (p=2.6E-1)

Phenotype Score: 0.504

Variant Score: 0.642

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-177092081-C-T [0/1] rs3135924
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.698 CONTRIBUTING VARIANT
Transcripts:
FGFR4:ENST00000292408.9:c.728-240C>T:p.(=)
Pathogenicity Data:
Best Score: 0.749834
REMM: 0.750
Frequency Data:
UK10K: 0.3174%
gnomAD_G_AFR: 0.0601%
gnomAD_G_AMR: 0.1764%
gnomAD_G_NFE: 0.3558%
gnomAD_G_SAS: 0.4146%
UPSTREAM_GENE_VARIANT DEL 5-177086802-TGG-T [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.586 CONTRIBUTING VARIANT
Transcripts:
FGFR4:ENST00000292408.9::
Pathogenicity Data:
Best Score: 0.586212
REMM: 0.586
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.065 (p=3.0E-1)

Phenotype Score: 0.504

Variant Score: 0.586

No phenotype matches to diseases with this MOI.
Variants contributing to score:
UPSTREAM_GENE_VARIANT DEL 5-177086802-TGG-T [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.586 CONTRIBUTING VARIANT
Transcripts:
FGFR4:ENST00000292408.9::
Pathogenicity Data:
Best Score: 0.586212
REMM: 0.586
Frequency Data:
No frequency data
Other passed variants:
INTERGENIC_VARIANT SNV 5-177074432-A-G [0/1] rs184434872
Variant score: 0.570
Transcripts:
FGFR4:ENST00000292408.9::
Pathogenicity Data:
Best Score: 0.668273
REMM: 0.668
Frequency Data:
UK10K: 0.4364%
gnomAD_G_AFR: 0.1107%
gnomAD_G_AMR: 0.5035%
gnomAD_G_NFE: 0.7350%
gnomAD_G_SAS: 0.6832%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 5-177096947-TTCCTCCTTC-T [0/1] rs1428958577
Variant score: 0.566
Transcripts:
FGFR4:ENST00000292408.9:c.2153+207_2153+215del:p.(=)
Pathogenicity Data:
Best Score: 0.565623
REMM: 0.566
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-177097009-C-T [0/1]
Variant score: 0.376
Transcripts:
FGFR4:ENST00000292408.9:c.2153+268C>T:p.(=)
Pathogenicity Data:
Best Score: 0.376392
REMM: 0.376
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 5-177069317-C-T [0/1] rs188136280
Variant score: 0.299
Transcripts:
FGFR4:ENST00000292408.9::
Pathogenicity Data:
Best Score: 0.368346
REMM: 0.368
Frequency Data:
UK10K: 0.4628%
gnomAD_G_AFR: 0.2295%
gnomAD_G_AMR: 0.8736%
gnomAD_G_NFE: 0.7878%
gnomAD_G_SAS: 0.7292%
UPSTREAM_GENE_VARIANT INS 5-177084675-A-ATATATATATATATTT [0/1] rs1268974802
Variant score: 0.293
Transcripts:
FGFR4:ENST00000292408.9::
Pathogenicity Data:
Best Score: 0.47386
REMM: 0.474
Frequency Data:
gnomAD_G_AFR: 0.0763%
gnomAD_G_AMR: 0.3988%
gnomAD_G_EAS: 1.3402%
gnomAD_G_NFE: 0.4193%
gnomAD_G_SAS: 0.4792%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-177094403-G-A [0/1] rs3135926
Variant score: 0.027
Transcripts:
FGFR4:ENST00000292408.9:c.1519+628G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0395583
REMM: 0.040
Frequency Data:
UK10K: 1.2298%
gnomAD_G_AFR: 0.1878%
gnomAD_G_AMR: 0.3856%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.1107%
gnomAD_G_SAS: 0.5604%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-177096982-T-C [0/1]
Variant score: 0.001
Transcripts:
FGFR4:ENST00000292408.9:c.2153+241T>C:p.(=)
Pathogenicity Data:
Best Score: 0.00116667
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-177094011-C-A [0/1] rs547819235
Variant score: 0.000
Transcripts:
FGFR4:ENST00000292408.9:c.1519+236C>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_NFE: 0.0118%
gnomAD_G_SAS: 0.0208%

PDE8B

Exomiser Score: 0.102 (p=2.6E-1)

Phenotype Score: 0.501

Variant Score: 0.642

Phenotype matches:
Proximity score 0.501 in interactome to GNAS and phenotypic similarity 0.998 to McCune-Albright syndrome associated with GNAS.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.501 in interactome to GNAS and phenotypic similarity 0.322 to mouse mutant of GNAS.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0014167, ectopic bone
HP:0006625, Multifocal breast carcinoma - MP:0014167, ectopic bone
Known diseases:
OMIM:609161 Striatal degeneration, autosomal dominant - autosomal dominant
OMIM:614190 Pigmented nodular adrenocortical disease, primary, 3 - autosomal dominant
ORPHA:228169 Autosomal dominant striatal neurodegeneration - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.102 (p=2.6E-1)

Phenotype Score: 0.501

Variant Score: 0.642

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 5-77259049-GAC-G [0/1] rs10552319
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.642 CONTRIBUTING VARIANT
Transcripts:
PDE8B:ENST00000264917.10:c.339+47786_339+47787del:p.(=)
Pathogenicity Data:
Best Score: 0.642004
REMM: 0.642
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.005 (p=5.4E-1)

Phenotype Score: 0.251

Variant Score: 0.594

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 5-77259049-GAC-G [0/1] rs10552319
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.642 CONTRIBUTING VARIANT
Transcripts:
PDE8B:ENST00000264917.10:c.339+47786_339+47787del:p.(=)
Pathogenicity Data:
Best Score: 0.642004
REMM: 0.642
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-77422635-T-A [0/1] rs887594514
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.546 CONTRIBUTING VARIANT
Transcripts:
PDE8B:ENST00000264917.10:c.2418+647T>A:p.(=)
Pathogenicity Data:
Best Score: 0.546921
REMM: 0.547
Frequency Data:
gnomAD_G_NFE: 0.0059%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 5-77415351-AT-A [0/1] rs71606293
Variant score: 0.429
Transcripts:
PDE8B:ENST00000264917.10:c.1911+2043del:p.(=)
Pathogenicity Data:
Best Score: 0.429145
REMM: 0.429
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 5-77386865-CT-C [1/1] rs59393259
Variant score: 0.235
Transcripts:
PDE8B:ENST00000264917.10:c.1168-13382del:p.(=)
Pathogenicity Data:
Best Score: 0.235232
REMM: 0.235
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-77289304-A-G [0/1] rs142397354
Variant score: 0.185
Transcripts:
PDE8B:ENST00000264917.10:c.340-22690A>G:p.(=)
Pathogenicity Data:
Best Score: 0.626104
REMM: 0.626
Frequency Data:
UK10K: 1.7720%
gnomAD_G_AFR: 0.2645%
gnomAD_G_AMR: 1.6222%
gnomAD_G_EAS: 0.0385%
gnomAD_G_NFE: 1.8255%
gnomAD_G_SAS: 1.0982%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 5-77378456-TAA-T [0/1] rs58121927
Variant score: 0.135
Transcripts:
PDE8B:ENST00000264917.10:c.1168-21791_1168-21790del:p.(=)
Pathogenicity Data:
Best Score: 0.135403
REMM: 0.135
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 5-77378456-TAAA-T [0/1] rs58121927
Variant score: 0.135
Transcripts:
PDE8B:ENST00000264917.10:c.1168-21791_1168-21789del:p.(=)
Pathogenicity Data:
Best Score: 0.135403
REMM: 0.135
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 5-77321142-AT-A [0/1] rs10538529
Variant score: 0.088
Transcripts:
PDE8B:ENST00000264917.10:c.400-4396del:p.(=)
Pathogenicity Data:
Best Score: 0.0883365
REMM: 0.088
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 5-77423632-G-GTTTTTTTTTTT [0/1] rs71594634
Variant score: 0.046
Transcripts:
PDE8B:ENST00000264917.10:c.2418+1644_2418+1645insTTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.275274
REMM: 0.275
Frequency Data:
gnomAD_G_AFR: 0.4276%
gnomAD_G_AMR: 0.7488%
gnomAD_G_EAS: 0.1113%
gnomAD_G_NFE: 1.9684%
gnomAD_G_SAS: 0.4323%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-77259085-A-C [1|1]
Variant score: 0.009
Transcripts:
PDE8B:ENST00000264917.10:c.339+47821A>C:p.(=)
Pathogenicity Data:
Best Score: 0.00942381
REMM: 0.009
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 5-77194717-G-A [0/1] rs72765172
Variant score: 0.001
Transcripts:
PDE8B:ENST00000264917.10::
Pathogenicity Data:
Best Score: 0.00178333
REMM: 0.002
Frequency Data:
UK10K: 1.1373%
gnomAD_G_AFR: 0.2024%
gnomAD_G_AMR: 0.5168%
gnomAD_G_NFE: 1.1985%
gnomAD_G_SAS: 0.2286%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 5-77367530-CT-C [0/1] rs3031815
Variant score: 0.001
Transcripts:
PDE8B:ENST00000264917.10:c.1167+14125del:p.(=)
Pathogenicity Data:
Best Score: 0.00106667
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-77395372-C-T [0/1] rs200920271
Variant score: 0.001
Transcripts:
PDE8B:ENST00000264917.10:c.1168-4876C>T:p.(=)
Pathogenicity Data:
Best Score: 0.001
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-77395351-A-G [0/1] rs13179191
Variant score: 0.001
Transcripts:
PDE8B:ENST00000264917.10:c.1168-4897A>G:p.(=)
Pathogenicity Data:
Best Score: 5.35714E-4
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-77309943-C-T [1/1] rs376537428
Variant score: 0.000
Transcripts:
PDE8B:ENST00000264917.10:c.340-2051C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-77356555-A-G [0/1] rs774721148
Variant score: 0.000
Transcripts:
PDE8B:ENST00000264917.10:c.1167+3149A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.0397%
gnomAD_G_AFR: 0.0072%
gnomAD_G_AMR: 0.0393%
gnomAD_G_NFE: 0.0839%
gnomAD_G_SAS: 0.0208%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-77395337-A-G [0/1] rs13179071
Variant score: 0.000
Transcripts:
PDE8B:ENST00000264917.10:c.1168-4911A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-77395367-A-G [0/1] rs13179196
Variant score: 0.000
Transcripts:
PDE8B:ENST00000264917.10:c.1168-4881A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-77395373-C-T [0/1] rs13159632
Variant score: 0.000
Transcripts:
PDE8B:ENST00000264917.10:c.1168-4875C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-77395390-T-C [0/1]
Variant score: 0.000
Transcripts:
PDE8B:ENST00000264917.10:c.1168-4858T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data

PAPSS2

Exomiser Score: 0.100 (p=2.6E-1)

Phenotype Score: 0.504

Variant Score: 0.637

Phenotype matches:
Phenotypic similarity 0.325 to mouse mutant involving PAPSS2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0008525, decreased cranium height
HP:0006625, Multifocal breast carcinoma - MP:0008525, decreased cranium height
Proximity score 0.504 in interactome to SEMA3A and phenotypic similarity 0.620 to Kallmann syndrome associated with SEMA3A.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003187, Breast hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0003187, Breast hypoplasia
Proximity score 0.504 in interactome to SEMA3A and phenotypic similarity 0.363 to mouse mutant of SEMA3A.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000150, abnormal rib morphology
HP:0006625, Multifocal breast carcinoma - MP:0000150, abnormal rib morphology
Known diseases:
OMIM:612847 Brachyolmia 4 with mild epiphyseal and metaphyseal changes - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.100 (p=2.6E-1)

Phenotype Score: 0.504

Variant Score: 0.637

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-87715306-G-T [0/1] rs184419483
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.704 CONTRIBUTING VARIANT
Transcripts:
PAPSS2:ENST00000456849.2:c.753+208G>T:p.(=)
Pathogenicity Data:
Best Score: 0.740815
REMM: 0.741
Frequency Data:
UK10K: 0.0397%
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.1242%
gnomAD_G_NFE: 0.0456%
gnomAD_G_SAS: 0.3113%
CODING_TRANSCRIPT_INTRON_VARIANT INS 10-87703276-C-CGTGTGTGT [0/1] rs10673718
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.570 CONTRIBUTING VARIANT
Transcripts:
PAPSS2:ENST00000456849.2:c.28-5920_28-5919insGTGTGTGT:p.(=)
Pathogenicity Data:
Best Score: 0.774244
REMM: 0.774
Frequency Data:
gnomAD_G_AFR: 0.1312%
gnomAD_G_AMR: 0.1702%
gnomAD_G_EAS: 0.3852%
gnomAD_G_NFE: 0.2018%
gnomAD_G_SAS: 1.0811%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.001 (p=7.4E-1)

Phenotype Score: 0.252

Variant Score: 0.385

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 10-87707564-CTTT-C [0/1] rs747152482
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.385 CONTRIBUTING VARIANT
Transcripts:
PAPSS2:ENST00000456849.2:c.28-1631_28-1629del:p.(=)
Pathogenicity Data:
Best Score: 0.385048
REMM: 0.385
Frequency Data:
No frequency data
Other passed variants:
INTERGENIC_VARIANT DEL 10-87643612-CAAAAAAAAAAAAAAAAAAAAAAAAAAA-C [0|1] rs71019490
Variant score: 0.458
Transcripts:
PAPSS2:ENST00000456849.2::
Pathogenicity Data:
Best Score: 0.478859
REMM: 0.479
Frequency Data:
gnomAD_G_AFR: 0.0666%
gnomAD_G_AMR: 0.2080%
gnomAD_G_NFE: 0.0999%
gnomAD_G_SAS: 0.2732%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 10-87706108-ATGTGTGTG-A [0/1] rs150079044
Variant score: 0.251
Transcripts:
PAPSS2:ENST00000456849.2:c.28-3087_28-3080del:p.(=)
Pathogenicity Data:
Best Score: 0.341014
REMM: 0.341
Frequency Data:
gnomAD_G_AFR: 1.0809%
gnomAD_G_AMR: 0.3870%
gnomAD_G_EAS: 0.3827%
gnomAD_G_NFE: 0.7903%
gnomAD_G_SAS: 0.2069%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 10-87697208-A-G [0/1] rs111959525
Variant score: 0.249
Transcripts:
PAPSS2:ENST00000456849.2:c.28-11988A>G:p.(=)
Pathogenicity Data:
Best Score: 0.471984
REMM: 0.472
Frequency Data:
UK10K: 1.4943%
gnomAD_G_AFR: 0.2889%
gnomAD_G_AMR: 0.7716%
gnomAD_G_NFE: 1.5028%
gnomAD_G_SAS: 0.2492%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 10-87706108-ATG-A [0/1] rs150079044
Variant score: 0.194
Transcripts:
PAPSS2:ENST00000456849.2:c.28-3087_28-3086del:p.(=)
Pathogenicity Data:
Best Score: 0.325276
REMM: 0.325
Frequency Data:
gnomAD_G_AFR: 1.3811%
gnomAD_G_AMR: 0.5077%
gnomAD_G_EAS: 1.0549%
gnomAD_G_NFE: 0.2142%
gnomAD_G_SAS: 0.1379%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 10-87736263-CT-C [0/1] rs10553485
Variant score: 0.159
Transcripts:
PAPSS2:ENST00000456849.2:c.1087-4971del:p.(=)
Pathogenicity Data:
Best Score: 0.158964
REMM: 0.159
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 10-87676872-CAAAAAAAAAAAA-C [1/1]
Variant score: 0.131
Transcripts:
PAPSS2:ENST00000456849.2:c.27+16865_27+16876del:p.(=)
Pathogenicity Data:
Best Score: 0.131473
REMM: 0.131
Frequency Data:
No frequency data
SYNONYMOUS_VARIANT SNV 10-87741315-C-T [0/1] rs145242127
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:1, LB:1)
Variant score: 0.095
Transcripts:
PAPSS2:ENST00000456849.2:c.1167C>T:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.0264%
gnomAD_E_AFR: 0.0060%
gnomAD_E_AMR: 0.0268%
gnomAD_E_NFE: 0.0209%
gnomAD_E_SAS: 0.2667%
gnomAD_G_AFR: 0.0072%
gnomAD_G_AMR: 0.1242%
gnomAD_G_NFE: 0.0456%
gnomAD_G_SAS: 0.3111%
THREE_PRIME_UTR_EXON_VARIANT INS 10-87746115-A-AT [0|1] rs369608774
Variant score: 0.033
Transcripts:
PAPSS2:ENST00000456849.2:c.*145_*146insT:p.(=)
Pathogenicity Data:
Best Score: 0.0358683
REMM: 0.036
Frequency Data:
gnomAD_E_AFR: 0.0080%
gnomAD_E_AMR: 0.1132%
gnomAD_E_EAS: 0.0110%
gnomAD_E_NFE: 0.0597%
gnomAD_E_SAS: 0.3468%
gnomAD_G_AFR: 0.0156%
gnomAD_G_AMR: 0.1863%
gnomAD_G_NFE: 0.0623%
gnomAD_G_SAS: 0.4506%

PEX5

Exomiser Score: 0.099 (p=2.6E-1)

Phenotype Score: 0.513

Variant Score: 0.627

Phenotype matches:
Phenotypic similarity 0.460 to Rhizomelic chondrodysplasia punctata, type 5 associated with PEX5.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0002943, Thoracic scoliosis
HP:0006625, Multifocal breast carcinoma - HP:0002943, Thoracic scoliosis
Proximity score 0.513 in interactome to PEX3 and phenotypic similarity 0.643 to ?Peroxisome biogenesis disorder 10B associated with PEX3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Proximity score 0.513 in interactome to PEX3 and phenotypic similarity 0.362 to mouse mutant of PEX3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000137, abnormal vertebrae morphology
HP:0006625, Multifocal breast carcinoma - MP:0000137, abnormal vertebrae morphology
Known diseases:
OMIM:202370 Peroxisome biogenesis disorder 2B - autosomal recessive
OMIM:214110 Peroxisome biogenesis disorder 2A (Zellweger) - autosomal recessive
OMIM:616716 Rhizomelic chondrodysplasia punctata, type 5 - autosomal recessive
ORPHA:44 Neonatal adrenoleukodystrophy - autosomal recessive
ORPHA:772 Infantile Refsum disease - autosomal recessive
ORPHA:912 Zellweger syndrome - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.099 (p=2.6E-1)

Phenotype Score: 0.513

Variant Score: 0.627

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.460 to OMIM:616716 Rhizomelic chondrodysplasia punctata, type 5
Variants contributing to score:
INTERGENIC_VARIANT SNV 12-7174734-A-G [0/1] rs137913759
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.628 CONTRIBUTING VARIANT
Transcripts:
PEX5:ENST00000675855.1::
Pathogenicity Data:
Best Score: 0.810931
REMM: 0.811
Frequency Data:
UK10K: 0.3967%
gnomAD_G_AFR: 0.1155%
gnomAD_G_AMR: 0.9804%
gnomAD_G_EAS: 0.0386%
gnomAD_G_NFE: 0.7204%
gnomAD_G_SAS: 0.3109%
INTERGENIC_VARIANT SNV 12-7220012-A-T [0/1] rs148199876
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.626 CONTRIBUTING VARIANT
Transcripts:
PEX5:ENST00000675855.1::
Pathogenicity Data:
Best Score: 0.822997
REMM: 0.823
Frequency Data:
UK10K: 0.5819%
gnomAD_G_AFR: 0.1252%
gnomAD_G_AMR: 1.0200%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.7102%
gnomAD_G_SAS: 0.8085%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.000 (p=8.5E-1)

Phenotype Score: 0.256

Variant Score: 0.264

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-7196597-GTAA-G [0/1] rs1346800099
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.264 CONTRIBUTING VARIANT
Transcripts:
PEX5:ENST00000675855.1:c.449-2413_449-2411del:p.(=)
Pathogenicity Data:
Best Score: 0.264332
REMM: 0.264
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-7196545-GTAA-G [0/1] rs1420649090
Variant score: 0.257
Transcripts:
PEX5:ENST00000675855.1:c.449-2465_449-2463del:p.(=)
Pathogenicity Data:
Best Score: 0.260492
REMM: 0.260
Frequency Data:
gnomAD_G_AFR: 0.0641%
gnomAD_G_AMR: 0.0637%
gnomAD_G_EAS: 0.1068%
gnomAD_G_NFE: 0.0865%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-7196549-TAATTA-T [0/1] rs373608841
Variant score: 0.256
Transcripts:
PEX5:ENST00000675855.1:c.449-2461_449-2457del:p.(=)
Pathogenicity Data:
Best Score: 0.26773
REMM: 0.268
Frequency Data:
gnomAD_G_AFR: 0.0092%
gnomAD_G_AMR: 0.0915%
gnomAD_G_NFE: 0.1238%
gnomAD_G_SAS: 0.2742%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-7196624-GTAA-G [0/1] rs368850795
Variant score: 0.235
Transcripts:
PEX5:ENST00000675855.1:c.449-2386_449-2384del:p.(=)
Pathogenicity Data:
Best Score: 0.235063
REMM: 0.235
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-7196643-C-T [1/1] rs62647644
Variant score: 0.208
Transcripts:
PEX5:ENST00000675855.1:c.449-2368C>T:p.(=)
Pathogenicity Data:
Best Score: 0.207858
REMM: 0.208
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-7196778-C-T [1/1] rs368863879
Variant score: 0.200
Transcripts:
PEX5:ENST00000675855.1:c.449-2233C>T:p.(=)
Pathogenicity Data:
Best Score: 0.199525
REMM: 0.200
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-7196670-C-T [1/1] rs62647645
Variant score: 0.190
Transcripts:
PEX5:ENST00000675855.1:c.449-2341C>T:p.(=)
Pathogenicity Data:
Best Score: 0.189662
REMM: 0.190
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-7196803-C-CAT [1/1] rs1491552489
Variant score: 0.184
Transcripts:
PEX5:ENST00000675855.1:c.449-2208_449-2207insAT:p.(=)
Pathogenicity Data:
Best Score: 0.183825
REMM: 0.184
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-7196751-C-T [1/1] rs868705186
Variant score: 0.178
Transcripts:
PEX5:ENST00000675855.1:c.449-2260C>T:p.(=)
Pathogenicity Data:
Best Score: 0.178469
REMM: 0.178
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-7196830-C-T [1/1] rs190911170
Variant score: 0.176
Transcripts:
PEX5:ENST00000675855.1:c.449-2181C>T:p.(=)
Pathogenicity Data:
Best Score: 0.175529
REMM: 0.176
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-7196697-C-T [1/1] rs373904045
Variant score: 0.175
Transcripts:
PEX5:ENST00000675855.1:c.449-2314C>T:p.(=)
Pathogenicity Data:
Best Score: 0.176314
REMM: 0.176
Frequency Data:
gnomAD_G_AFR: 0.0551%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-7196805-C-T [1/1] rs866629027
Variant score: 0.162
Transcripts:
PEX5:ENST00000675855.1:c.449-2206C>T:p.(=)
Pathogenicity Data:
Best Score: 0.162212
REMM: 0.162
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-7196724-C-T [1/1] rs377355453
Variant score: 0.145
Transcripts:
PEX5:ENST00000675855.1:c.449-2287C>T:p.(=)
Pathogenicity Data:
Best Score: 0.195392
REMM: 0.195
Frequency Data:
gnomAD_G_AMR: 1.0638%
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-7197109-C-CAT [1/1] rs199516031
Variant score: 0.094
Transcripts:
PEX5:ENST00000675855.1:c.449-1902_449-1901insAT:p.(=)
Pathogenicity Data:
Best Score: 0.112399
REMM: 0.112
Frequency Data:
gnomAD_G_AFR: 0.4184%
gnomAD_G_AMR: 0.8065%
gnomAD_G_EAS: 0.1984%
gnomAD_G_NFE: 0.1080%
DOWNSTREAM_GENE_VARIANT SNV 12-7213635-C-G [0/1] rs796145940
Variant score: 0.085
Transcripts:
PEX5:ENST00000675855.1::
Pathogenicity Data:
Best Score: 0.108461
REMM: 0.108
Frequency Data:
gnomAD_G_AFR: 0.1164%
gnomAD_G_AMR: 0.9596%
gnomAD_G_EAS: 0.0388%
gnomAD_G_NFE: 0.7083%
gnomAD_G_SAS: 0.3713%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-7197087-C-T [1/1] rs183788249
Variant score: 0.062
Transcripts:
PEX5:ENST00000675855.1:c.449-1924C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0627
REMM: 0.063
Frequency Data:
gnomAD_G_NFE: 0.0271%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-7196616-C-T [1/1] rs62647643
Variant score: 0.052
Transcripts:
PEX5:ENST00000675855.1:c.449-2395C>T:p.(=)
Pathogenicity Data:
Best Score: 0.18997
REMM: 0.190
Frequency Data:
gnomAD_G_AFR: 1.8519%
DOWNSTREAM_GENE_VARIANT INS 12-7213463-A-AAAAC [1/1] rs770678441
Variant score: 0.014
Transcripts:
PEX5:ENST00000675855.1::
Pathogenicity Data:
Best Score: 0.0135845
REMM: 0.014
Frequency Data:
No frequency data
INTERGENIC_VARIANT INS 12-7174018-T-TTCTC [0/1]
Variant score: 0.001
Transcripts:
PEX5:ENST00000675855.1::
Pathogenicity Data:
Best Score: 0.00143333
REMM: 0.001
Frequency Data:
No frequency data

HNF4A

Exomiser Score: 0.099 (p=2.7E-1)

Phenotype Score: 0.502

Variant Score: 0.638

Phenotype matches:
Proximity score 0.502 in interactome to NR5A1 and phenotypic similarity 0.676 to 46,XX gonadal dysgenesis associated with NR5A1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
HP:0006625, Multifocal breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
Known diseases:
OMIM:125850 MODY, type I - autosomal dominant
OMIM:125853 Diabetes mellitus, noninsulin-dependent (susceptibility)
OMIM:616026 Fanconi renotubular syndrome 4, with maturity-onset diabetes of the young - autosomal dominant
ORPHA:552 MODY - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.099 (p=2.7E-1)

Phenotype Score: 0.502

Variant Score: 0.638

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 20-44404972-T-TG [0/1] rs1253170622
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.638 CONTRIBUTING VARIANT
Transcripts:
HNF4A:ENST00000316673.9:c.50-1086_50-1085insG:p.(=)
Pathogenicity Data:
Best Score: 0.63815
REMM: 0.638
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.004 (p=5.6E-1)

Phenotype Score: 0.251

Variant Score: 0.573

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 20-44404972-T-TG [0/1] rs1253170622
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.638 CONTRIBUTING VARIANT
Transcripts:
HNF4A:ENST00000316673.9:c.50-1086_50-1085insG:p.(=)
Pathogenicity Data:
Best Score: 0.63815
REMM: 0.638
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 20-44404947-GGA-G [0/1] rs1283618712
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.507 CONTRIBUTING VARIANT
Transcripts:
HNF4A:ENST00000316673.9:c.50-1110_50-1109del:p.(=)
Pathogenicity Data:
Best Score: 0.513069
REMM: 0.513
Frequency Data:
gnomAD_G_AFR: 0.0172%
gnomAD_G_AMR: 0.0469%
gnomAD_G_NFE: 0.0041%
gnomAD_G_SAS: 0.0805%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT INS 20-44404783-G-GTTGA [0/1] rs141054050
Variant score: 0.458
Transcripts:
HNF4A:ENST00000316673.9:c.50-1275_50-1274insTTGA:p.(=)
Pathogenicity Data:
Best Score: 0.463479
REMM: 0.463
Frequency Data:
gnomAD_G_AFR: 0.0086%
gnomAD_G_EAS: 0.0816%
gnomAD_G_NFE: 0.0232%
CODING_TRANSCRIPT_INTRON_VARIANT INS 20-44385869-G-GT [0/1] rs771753314
Variant score: 0.229
Transcripts:
HNF4A:ENST00000316673.9:c.50-20189_50-20188insT:p.(=)
Pathogenicity Data:
Best Score: 0.254565
REMM: 0.255
Frequency Data:
gnomAD_G_AFR: 0.4301%
gnomAD_G_AMR: 0.3106%
gnomAD_G_EAS: 0.0196%
gnomAD_G_NFE: 0.5522%
gnomAD_G_SAS: 0.2104%
INTERGENIC_VARIANT SNV 20-44448103-G-T [0/1] rs142094782
Variant score: 0.168
Transcripts:
HNF4A:ENST00000316673.9::
Pathogenicity Data:
Best Score: 0.208746
REMM: 0.209
Frequency Data:
UK10K: 0.8199%
gnomAD_G_AFR: 0.1180%
gnomAD_G_AMR: 0.2879%
gnomAD_G_EAS: 0.0387%
gnomAD_G_NFE: 0.8896%
gnomAD_G_SAS: 0.6661%
CODING_TRANSCRIPT_INTRON_VARIANT INS 20-44404799-G-GC [0/1] rs1197266533
Variant score: 0.166
Transcripts:
HNF4A:ENST00000316673.9:c.50-1259_50-1258insC:p.(=)
Pathogenicity Data:
Best Score: 0.166382
REMM: 0.166
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 20-44438219-A-G [0/1] rs867311210
Variant score: 0.104
Transcripts:
HNF4A:ENST00000316673.9::
Pathogenicity Data:
Best Score: 0.103592
REMM: 0.104
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 20-44437991-GA-G [0/1] rs1395894117
Variant score: 0.080
Transcripts:
HNF4A:ENST00000316673.9::
Pathogenicity Data:
Best Score: 0.0798758
REMM: 0.080
Frequency Data:
No frequency data
INTERGENIC_VARIANT INS 20-44437966-T-TTATATATTTA [0/1]
Variant score: 0.079
Transcripts:
HNF4A:ENST00000316673.9::
Pathogenicity Data:
Best Score: 0.0788464
REMM: 0.079
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 20-44404825-A-G [1/1]
Variant score: 0.078
Transcripts:
HNF4A:ENST00000316673.9:c.50-1233A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0777829
REMM: 0.078
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 20-44387655-C-CG [0/1]
Variant score: 0.075
Transcripts:
HNF4A:ENST00000316673.9:c.50-18403_50-18402insG:p.(=)
Pathogenicity Data:
Best Score: 0.075044
REMM: 0.075
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 20-44438174-G-A [0/1] rs189543089
Variant score: 0.048
Transcripts:
HNF4A:ENST00000316673.9::
Pathogenicity Data:
Best Score: 0.0490337
REMM: 0.049
Frequency Data:
gnomAD_G_AFR: 0.1513%
gnomAD_G_NFE: 0.0684%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 20-44379730-CTT-C [1/1] rs33924202
Variant score: 0.044
Transcripts:
HNF4A:ENST00000316673.9:c.49+23878_49+23879del:p.(=)
Pathogenicity Data:
Best Score: 0.0438603
REMM: 0.044
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 20-44438204-G-A [0/1] rs186887338
Variant score: 0.040
Transcripts:
HNF4A:ENST00000316673.9::
Pathogenicity Data:
Best Score: 0.044756
REMM: 0.045
Frequency Data:
gnomAD_G_AFR: 0.1502%
gnomAD_G_NFE: 0.0627%
gnomAD_G_SAS: 0.5814%
CODING_TRANSCRIPT_INTRON_VARIANT INS 20-44368160-A-ATTT [0/1]
Variant score: 0.027
Transcripts:
HNF4A:ENST00000316673.9:c.49+12307_49+12308insTTT:p.(=)
Pathogenicity Data:
Best Score: 0.0274234
REMM: 0.027
Frequency Data:
No frequency data

FOXP2

Exomiser Score: 0.091 (p=2.7E-1)

Phenotype Score: 0.501

Variant Score: 0.628

Phenotype matches:
Proximity score 0.501 in interactome to CCDC141 and phenotypic similarity 0.620 to Kallmann syndrome associated with CCDC141.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003187, Breast hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0003187, Breast hypoplasia
Known diseases:
OMIM:602081 Speech-language disorder-1 - autosomal dominant
ORPHA:209908 Isolated childhood apraxia of speech - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.091 (p=2.7E-1)

Phenotype Score: 0.501

Variant Score: 0.628

No phenotype matches to diseases with this MOI.
Variants contributing to score:
INTERGENIC_VARIANT DEL 7-114712881-CCAGGA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.628 CONTRIBUTING VARIANT
Transcripts:
FOXP2:ENST00000350908.9::
Pathogenicity Data:
Best Score: 0.628251
REMM: 0.628
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.005 (p=5.5E-1)

Phenotype Score: 0.251

Variant Score: 0.584

No phenotype matches to diseases with this MOI.
Variants contributing to score:
INTERGENIC_VARIANT DEL 7-114712881-CCAGGA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.628 CONTRIBUTING VARIANT
Transcripts:
FOXP2:ENST00000350908.9::
Pathogenicity Data:
Best Score: 0.628251
REMM: 0.628
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-114643558-G-A [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.539 CONTRIBUTING VARIANT
Transcripts:
FOXP2:ENST00000350908.9:c.989+935G>A:p.(=)
Pathogenicity Data:
Best Score: 0.539017
REMM: 0.539
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-114467719-A-T [0/1] rs571576498
Variant score: 0.496
Transcripts:
FOXP2:ENST00000350908.9:c.168+41040A>T:p.(=)
Pathogenicity Data:
Best Score: 0.657957
REMM: 0.658
Frequency Data:
gnomAD_G_AMR: 0.0327%
gnomAD_G_NFE: 0.0103%
gnomAD_G_SAS: 1.0356%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-114587883-C-G [1|1] rs200083890
Variant score: 0.492
Transcripts:
FOXP2:ENST00000350908.9:c.259-40657C>G:p.(=)
Pathogenicity Data:
Best Score: 0.492126
REMM: 0.492
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-114556416-C-A [0/1] rs138409473
Variant score: 0.364
Transcripts:
FOXP2:ENST00000350908.9:c.258+21710C>A:p.(=)
Pathogenicity Data:
Best Score: 0.930739
REMM: 0.931
Frequency Data:
UK10K: 0.9786%
gnomAD_G_AFR: 0.1540%
gnomAD_G_AMR: 0.1046%
gnomAD_G_NFE: 0.6955%
gnomAD_G_SAS: 1.7041%
INTERGENIC_VARIANT INS 7-114699876-A-AAAAGAAAGAAAGAAAGAAAGAAAGAAAG [0/1] rs71149753
Variant score: 0.064
Transcripts:
FOXP2:ENST00000350908.9::
Pathogenicity Data:
Best Score: 0.0641349
REMM: 0.064
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-114646060-T-TAAAAA [1/1] rs57137258
Variant score: 0.005
Transcripts:
FOXP2:ENST00000350908.9:c.1094+1271_1094+1272insAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.00492222
REMM: 0.005
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-114592433-C-T [0/1]
Variant score: 0.001
Transcripts:
FOXP2:ENST00000350908.9:c.259-36107C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00107143
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 7-114479058-G-A [0/1] rs573065196
Variant score: 0.000
Transcripts:
FOXP2:ENST00000350908.9:c.168+52379G>A:p.(=)
Pathogenicity Data:
Best Score: 4.92857E-4
REMM: 0.000
Frequency Data:
UK10K: 0.7141%
gnomAD_G_AFR: 0.1303%
gnomAD_G_AMR: 0.0330%
gnomAD_G_NFE: 0.4794%
gnomAD_G_SAS: 1.6632%

SPTA1

Exomiser Score: 0.087 (p=2.8E-1)

Phenotype Score: 0.505

Variant Score: 0.619

Phenotype matches:
Phenotypic similarity 0.285 to mouse mutant involving SPTA1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002397, abnormal bone marrow morphology
HP:0006625, Multifocal breast carcinoma - MP:0002397, abnormal bone marrow morphology
Proximity score 0.505 in interactome to SPTBN1 and phenotypic similarity 0.685 to Developmental delay, impaired speech, and behavioral abnormalities associated with SPTBN1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0032408, Breast mass
HP:0006625, Multifocal breast carcinoma - HP:0032408, Breast mass
Known diseases:
OMIM:130600 Elliptocytosis-2 - autosomal dominant
OMIM:266140 Pyropoikilocytosis - autosomal recessive
OMIM:270970 Spherocytosis, type 3 - autosomal recessive
ORPHA:288 Hereditary elliptocytosis - autosomal dominant
ORPHA:822 Hereditary spherocytosis - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.087 (p=2.8E-1)

Phenotype Score: 0.505

Variant Score: 0.619

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-158650458-C-G [0/1] rs946167061
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.619 CONTRIBUTING VARIANT
Transcripts:
SPTA1:ENST00000643759.2:c.3478-511G>C:p.(=)
Pathogenicity Data:
Best Score: 0.619767
REMM: 0.620
Frequency Data:
gnomAD_G_NFE: 0.0044%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.080 (p=2.8E-1)

Phenotype Score: 0.505

Variant Score: 0.609

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-158650458-C-G [0/1] rs946167061
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.619 CONTRIBUTING VARIANT
Transcripts:
SPTA1:ENST00000643759.2:c.3478-511G>C:p.(=)
Pathogenicity Data:
Best Score: 0.619767
REMM: 0.620
Frequency Data:
gnomAD_G_NFE: 0.0044%
MISSENSE_VARIANT SNV 1-158672144-C-T [0/1] rs372937123
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.598 CONTRIBUTING VARIANT
Transcripts:
SPTA1:ENST00000643759.2:c.1403G>A:p.(Arg468His)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 0.0120%
gnomAD_E_NFE: 0.0013%
gnomAD_E_SAS: 0.0012%
gnomAD_G_AFR: 0.0241%
gnomAD_G_AMR: 0.0065%
gnomAD_G_EAS: 0.0192%
gnomAD_G_SAS: 0.0207%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-158659595-A-ATTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT [0/1] rs1177353050
Variant score: 0.465
Transcripts:
SPTA1:ENST00000643759.2:c.2587+1691_2587+1692insAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.4659
REMM: 0.466
Frequency Data:
gnomAD_G_NFE: 0.0067%
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-158659595-A-ATTTTTTTTTTTTTTTTTTTTTT [0/1] rs1177353050
Variant score: 0.462
Transcripts:
SPTA1:ENST00000643759.2:c.2587+1691_2587+1692insAAAAAAAAAAAAAAAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.4659
REMM: 0.466
Frequency Data:
gnomAD_G_AFR: 0.0040%
gnomAD_G_NFE: 0.0666%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-158652022-A-T [0/1] rs745745512
Variant score: 0.000
Transcripts:
SPTA1:ENST00000643759.2:c.3375+445T>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.0132%
gnomAD_G_NFE: 0.0044%

GDAP1

Exomiser Score: 0.081 (p=2.8E-1)

Phenotype Score: 0.504

Variant Score: 0.611

Phenotype matches:
Phenotypic similarity 0.504 to Autosomal recessive Charcot-Marie-Tooth disease with hoarseness associated with GDAP1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000765, Abnormal thorax morphology
HP:0006625, Multifocal breast carcinoma - HP:0000765, Abnormal thorax morphology
Proximity score 0.500 in interactome to SOX10 and phenotypic similarity 0.620 to Kallmann syndrome associated with SOX10.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003187, Breast hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0003187, Breast hypoplasia
Proximity score 0.500 in interactome to SOX10 and phenotypic similarity 0.310 to mouse mutant of SOX10.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0004493, dilated cochlea
HP:0006625, Multifocal breast carcinoma - MP:0004493, dilated cochlea
Proximity score 0.500 in interactome to SOX10 and phenotypic similarity 0.300 to fish mutant of SOX10.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0018830, perichondrium disorganized, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0018830, perichondrium disorganized, abnormal
Known diseases:
OMIM:214400 Charcot-Marie-Tooth disease, type 4A - autosomal recessive
OMIM:607706 Charcot-Marie-Tooth disease, axonal, with vocal cord paresis - autosomal recessive
OMIM:607831 Charcot-Marie-Tooth disease, axonal, type 2K - autosomal dominant/recessive
OMIM:608340 Charcot-Marie-Tooth disease, recessive intermediate, A - autosomal recessive
ORPHA:101097 Autosomal recessive Charcot-Marie-Tooth disease with hoarseness - autosomal recessive
ORPHA:101097 Autosomal recessive Charcot-Marie-Tooth disease with hoarseness - autosomal dominant/recessive
ORPHA:99944 Autosomal dominant Charcot-Marie-Tooth disease type 2K - autosomal dominant/recessive
ORPHA:99948 Charcot-Marie-Tooth disease type 4A - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.081 (p=2.8E-1)

Phenotype Score: 0.504

Variant Score: 0.611

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.504 to ORPHA:101097 Autosomal recessive Charcot-Marie-Tooth disease with hoarseness
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-74355688-A-T [0/1] rs369958522
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.627 CONTRIBUTING VARIANT
Transcripts:
GDAP1:ENST00000220822.12:c.310+4222A>T:p.(=)
Pathogenicity Data:
Best Score: 0.644388
REMM: 0.644
Frequency Data:
UK10K: 0.0793%
gnomAD_G_AFR: 0.0216%
gnomAD_G_AMR: 0.0327%
gnomAD_G_NFE: 0.1338%
gnomAD_G_SAS: 0.1863%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-74351815-A-G [0/1] rs776797601
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.596 CONTRIBUTING VARIANT
Transcripts:
GDAP1:ENST00000220822.12:c.310+349A>G:p.(=)
Pathogenicity Data:
Best Score: 0.600985
REMM: 0.601
Frequency Data:
UK10K: 0.0132%
gnomAD_G_NFE: 0.0147%
gnomAD_G_SAS: 0.0622%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.071 (p=2.9E-1)

Phenotype Score: 0.504

Variant Score: 0.596

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.504 to ORPHA:101097 Autosomal recessive Charcot-Marie-Tooth disease with hoarseness
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-74351815-A-G [0/1] rs776797601
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.596 CONTRIBUTING VARIANT
Transcripts:
GDAP1:ENST00000220822.12:c.310+349A>G:p.(=)
Pathogenicity Data:
Best Score: 0.600985
REMM: 0.601
Frequency Data:
UK10K: 0.0132%
gnomAD_G_NFE: 0.0147%
gnomAD_G_SAS: 0.0622%
Other passed variants:
DOWNSTREAM_GENE_VARIANT SNV 8-74371207-T-C [0/1] rs373074541
Variant score: 0.536
Transcripts:
GDAP1:ENST00000220822.12::
Pathogenicity Data:
Best Score: 0.551761
REMM: 0.552
Frequency Data:
gnomAD_G_AFR: 0.0216%
gnomAD_G_AMR: 0.0261%
gnomAD_G_NFE: 0.1338%
gnomAD_G_SAS: 0.1866%
INTERGENIC_VARIANT SNV 8-74384755-C-T [0/1] rs375538618
Variant score: 0.000
Transcripts:
GDAP1:ENST00000220822.12::
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.0793%
gnomAD_G_AFR: 0.0794%
gnomAD_G_AMR: 0.0262%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.1073%
gnomAD_G_SAS: 0.1244%

SLC3A1

Exomiser Score: 0.080 (p=2.8E-1)

Phenotype Score: 0.502

Variant Score: 0.612

Phenotype matches:
Phenotypic similarity 0.319 to mouse mutant involving SLC3A1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000063, decreased bone mineral density
HP:0006625, Multifocal breast carcinoma - MP:0000063, decreased bone mineral density
Proximity score 0.502 in interactome to POLD1 and phenotypic similarity 0.998 to Polymerase proofreading-related adenomatous polyposis associated with POLD1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.502 in interactome to POLD1 and phenotypic similarity 0.260 to fish mutant of POLD1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0001988, neurocranium decreased size, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0001988, neurocranium decreased size, abnormal
Known diseases:
OMIM:220100 Cystinuria - autosomal dominant/recessive
ORPHA:163690 Hypotonia-cystinuria syndrome (CNV)
ORPHA:163693 2p21 microdeletion syndrome (CNV)
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.080 (p=2.8E-1)

Phenotype Score: 0.502

Variant Score: 0.612

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 2-44315653-C-CAA [1/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.612 CONTRIBUTING VARIANT
Transcripts:
SLC3A1:ENST00000260649.11:c.1617+1702_1617+1703insAA:p.(=)
Pathogenicity Data:
Best Score: 0.612454
REMM: 0.612
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.003 (p=6.0E-1)

Phenotype Score: 0.502

Variant Score: 0.245

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 2-44277104-T-TTC [0|1] rs1491285872
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.245 CONTRIBUTING VARIANT
Transcripts:
SLC3A1:ENST00000260649.11:c.430+1139_430+1140insTC:p.(=)
Pathogenicity Data:
Best Score: 0.245042
REMM: 0.245
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 2-44305427-CT-C [0/1] rs139686441
Variant score: 0.067
Transcripts:
SLC3A1:ENST00000260649.11:c.1332+1090del:p.(=)
Pathogenicity Data:
Best Score: 0.0673
REMM: 0.067
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 2-44318094-TG-T [0/1] rs781080384
Variant score: 0.000
Transcripts:
SLC3A1:ENST00000260649.11:c.1618-2104del:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_E_AFR: 1.3066%
gnomAD_E_AMR: 0.0520%
gnomAD_E_NFE: 0.0052%
gnomAD_E_SAS: 0.0155%
gnomAD_G_AFR: 0.2235%
gnomAD_G_AMR: 0.0234%
gnomAD_G_NFE: 0.0148%

NOTCH1

Exomiser Score: 0.080 (p=2.8E-1)

Phenotype Score: 0.515

Variant Score: 0.598

Phenotype matches:
Phenotypic similarity 0.368 to mouse mutant involving NOTCH1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000137, abnormal vertebrae morphology
HP:0006625, Multifocal breast carcinoma - MP:0000137, abnormal vertebrae morphology
Proximity score 0.515 in interactome to EBF3 and phenotypic similarity 0.643 to Hypotonia, ataxia, and delayed development syndrome associated with EBF3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Known diseases:
OMIM:109730 Aortic valve disease 1 - autosomal dominant
OMIM:616028 Adams-Oliver syndrome 5 - autosomal dominant
ORPHA:402075 Familial bicuspid aortic valve - autosomal dominant
ORPHA:974 Adams-Oliver syndrome - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.080 (p=2.8E-1)

Phenotype Score: 0.515

Variant Score: 0.598

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 9-136497363-C-T [0/1] rs572960572
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:2, LB:1)
Variant score: 0.598 CONTRIBUTING VARIANT
Transcripts:
NOTCH1:ENST00000651671.1:c.6376G>A:p.(Gly2126Arg)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 0.0120%
gnomAD_E_AMR: 0.0112%
gnomAD_E_NFE: 0.0055%
gnomAD_E_SAS: 0.0058%
gnomAD_G_AFR: 0.0096%
gnomAD_G_AMR: 0.0065%
gnomAD_G_NFE: 0.0265%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.004 (p=5.7E-1)

Phenotype Score: 0.257

Variant Score: 0.558

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 9-136497363-C-T [0/1] rs572960572
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:2, LB:1)
Variant score: 0.598 CONTRIBUTING VARIANT
Transcripts:
NOTCH1:ENST00000651671.1:c.6376G>A:p.(Gly2126Arg)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 0.0120%
gnomAD_E_AMR: 0.0112%
gnomAD_E_NFE: 0.0055%
gnomAD_E_SAS: 0.0058%
gnomAD_G_AFR: 0.0096%
gnomAD_G_AMR: 0.0065%
gnomAD_G_NFE: 0.0265%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 9-136528398-GGGA-G [0/1] rs67578972
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.519 CONTRIBUTING VARIANT
Transcripts:
NOTCH1:ENST00000651671.1:c.141-4422_141-4420del:p.(=)
Pathogenicity Data:
Best Score: 0.519118
REMM: 0.519
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 9-136535569-GGA-G [0/1] rs1409860897
Variant score: 0.454
Transcripts:
NOTCH1:ENST00000651671.1:c.140+8453_140+8454del:p.(=)
Pathogenicity Data:
Best Score: 0.453844
REMM: 0.454
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-136535732-G-A [0/1] rs80069947
Variant score: 0.428
Transcripts:
NOTCH1:ENST00000651671.1:c.140+8292C>T:p.(=)
Pathogenicity Data:
Best Score: 0.428437
REMM: 0.428
Frequency Data:
No frequency data
DOWNSTREAM_GENE_VARIANT DEL 9-136490154-CT-C [1/1] rs71384084
Variant score: 0.182
Transcripts:
NOTCH1:ENST00000651671.1::
Pathogenicity Data:
Best Score: 0.182463
REMM: 0.182
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 9-136535622-GAGA-G [0/1] rs751009512
Variant score: 0.151
Transcripts:
NOTCH1:ENST00000651671.1:c.140+8399_140+8401del:p.(=)
Pathogenicity Data:
Best Score: 0.30199
REMM: 0.302
Frequency Data:
UK10K: 1.5472%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 9-136528416-GC-G [0/1]
Variant score: 0.090
Transcripts:
NOTCH1:ENST00000651671.1:c.141-4438del:p.(=)
Pathogenicity Data:
Best Score: 0.0899714
REMM: 0.090
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-136534900-T-C [0/1]
Variant score: 0.028
Transcripts:
NOTCH1:ENST00000651671.1:c.140+9124A>G:p.(=)
Pathogenicity Data:
Best Score: 0.027521
REMM: 0.028
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-136534913-G-C [0/1]
Variant score: 0.016
Transcripts:
NOTCH1:ENST00000651671.1:c.140+9111C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0159266
REMM: 0.016
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-136509316-G-A [0/1] rs11574900
Variant score: 0.000
Transcripts:
NOTCH1:ENST00000651671.1:c.2970-245C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.6876%
gnomAD_G_AFR: 0.1252%
gnomAD_G_AMR: 0.5620%
gnomAD_G_NFE: 0.7247%
gnomAD_G_SAS: 0.3524%

DICER1

Exomiser Score: 0.079 (p=2.8E-1)

Phenotype Score: 0.505

Variant Score: 0.608

Phenotype matches:
Phenotypic similarity 0.444 to GLOW syndrome, somatic mosaic associated with DICER1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000767, Pectus excavatum
HP:0006625, Multifocal breast carcinoma - HP:0000767, Pectus excavatum
Phenotypic similarity 0.284 to zebrafish mutant involving DICER1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0003089, splanchnocranium morphology, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0003089, splanchnocranium morphology, abnormal
Proximity score 0.505 in interactome to RAD51C and phenotypic similarity 0.998 to Hereditary breast and/or ovarian cancer syndrome associated with RAD51C.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Known diseases:
OMIM:138800 Goiter, multinodular 1, with or without Sertoli-Leydig cell tumors - autosomal dominant
OMIM:180295 Rhabdomyosarcoma, embryonal, 2 - unknown
OMIM:601200 Pleuropulmonary blastoma - autosomal dominant
OMIM:618272 GLOW syndrome, somatic mosaic - somatic
ORPHA:276399 Familial multinodular goiter (susceptibility)
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.079 (p=2.8E-1)

Phenotype Score: 0.505

Variant Score: 0.608

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-95125570-A-G [0/1] rs868168097
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.608 CONTRIBUTING VARIANT
Transcripts:
DICER1:ENST00000343455.8:c.904-902T>C:p.(=)
Pathogenicity Data:
Best Score: 0.608725
REMM: 0.609
Frequency Data:
gnomAD_G_NFE: 0.0031%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.003 (p=6.2E-1)

Phenotype Score: 0.252

Variant Score: 0.514

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-95125570-A-G [0/1] rs868168097
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.608 CONTRIBUTING VARIANT
Transcripts:
DICER1:ENST00000343455.8:c.904-902T>C:p.(=)
Pathogenicity Data:
Best Score: 0.608725
REMM: 0.609
Frequency Data:
gnomAD_G_NFE: 0.0031%
FIVE_PRIME_UTR_INTRON_VARIANT INS 14-95136086-T-TACACACAC [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.420 CONTRIBUTING VARIANT
Transcripts:
DICER1:ENST00000343455.8:c.-45-2584_-45-2583insGTGTGTGT:p.(=)
Pathogenicity Data:
Best Score: 0.420096
REMM: 0.420
Frequency Data:
No frequency data
Other passed variants:
FIVE_PRIME_UTR_INTRON_VARIANT SNV 14-95147227-G-A [0/1]
Variant score: 0.412
Transcripts:
DICER1:ENST00000343455.8:c.-46+10003C>T:p.(=)
Pathogenicity Data:
Best Score: 0.411554
REMM: 0.412
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 14-95125505-GGA-G [0/1] rs368421768
Variant score: 0.011
Transcripts:
DICER1:ENST00000343455.8:c.904-839_904-838del:p.(=)
Pathogenicity Data:
Best Score: 0.0144052
REMM: 0.014
Frequency Data:
gnomAD_G_AFR: 0.0336%
gnomAD_G_AMR: 0.4148%
gnomAD_G_NFE: 0.1956%
gnomAD_G_SAS: 0.9239%
THREE_PRIME_UTR_EXON_VARIANT SNV 14-95088448-C-G [0/1] rs182848457
ClinVar: BENIGN (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.001
Transcripts:
DICER1:ENST00000343455.8:c.*2050G>C:p.(=)
Pathogenicity Data:
Best Score: 0.0022
REMM: 0.002
Frequency Data:
UK10K: 0.1851%
gnomAD_E_AFR: 0.0788%
gnomAD_E_AMR: 0.4870%
gnomAD_E_NFE: 0.3283%
gnomAD_E_SAS: 1.0057%
gnomAD_G_AFR: 0.0505%
gnomAD_G_AMR: 0.7192%
gnomAD_G_NFE: 0.2249%
gnomAD_G_SAS: 1.2225%

FREM2

Exomiser Score: 0.077 (p=2.9E-1)

Phenotype Score: 0.569

Variant Score: 0.532

Phenotype matches:
Phenotypic similarity 0.569 to Fraser syndrome associated with FREM2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0006610, Wide intermamillary distance
HP:0006625, Multifocal breast carcinoma - HP:0006610, Wide intermamillary distance
Phenotypic similarity 0.319 to mouse mutant involving FREM2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0003104, acrania
HP:0006625, Multifocal breast carcinoma - MP:0003104, acrania
Known diseases:
OMIM:123570 Cryptophthalmos, unilateral or bilateral, isolated - autosomal recessive
OMIM:617666 Fraser syndrome 2 - autosomal recessive
ORPHA:2052 Fraser syndrome - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.077 (p=2.9E-1)

Phenotype Score: 0.569

Variant Score: 0.532

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.569 to ORPHA:2052 Fraser syndrome
Phenotypic similarity 0.548 to OMIM:617666 Fraser syndrome 2
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 13-38715580-A-G [0/1] rs1041917518
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.555 CONTRIBUTING VARIANT
Transcripts:
FREM2:ENST00000280481.9:c.5263+17793A>G:p.(=)
Pathogenicity Data:
Best Score: 0.566789
REMM: 0.567
Frequency Data:
gnomAD_G_NFE: 0.0250%
gnomAD_G_SAS: 0.1456%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 13-38756524-CT-C [0/1] rs1187227144
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.510 CONTRIBUTING VARIANT
Transcripts:
FREM2:ENST00000280481.9:c.5264-7779del:p.(=)
Pathogenicity Data:
Best Score: 0.510211
REMM: 0.510
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.001 (p=7.2E-1)

Phenotype Score: 0.159

Variant Score: 0.510

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 13-38756524-CT-C [0/1] rs1187227144
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.510 CONTRIBUTING VARIANT
Transcripts:
FREM2:ENST00000280481.9:c.5264-7779del:p.(=)
Pathogenicity Data:
Best Score: 0.510211
REMM: 0.510
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT INS 13-38763464-C-CTTTTTTTTTTTT [1|1]
Variant score: 0.527
Transcripts:
FREM2:ENST00000280481.9:c.5264-840_5264-839insTTTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.52734
REMM: 0.527
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 13-38738565-CA-C [0/1]
Variant score: 0.460
Transcripts:
FREM2:ENST00000280481.9:c.5264-25738del:p.(=)
Pathogenicity Data:
Best Score: 0.459544
REMM: 0.460
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 13-38858992-G-A [0/1] rs8002781
ClinVar: BENIGN (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.450
Transcripts:
FREM2:ENST00000280481.9:c.7216-295G>A:p.(=)
Pathogenicity Data:
Best Score: 0.449878
REMM: 0.450
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 13-38738568-A-AT [0/1] rs368021771
Variant score: 0.418
Transcripts:
FREM2:ENST00000280481.9:c.5264-25736_5264-25735insT:p.(=)
Pathogenicity Data:
Best Score: 0.417694
REMM: 0.418
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 13-38822251-G-A [0/1] rs544185297
Variant score: 0.388
Transcripts:
FREM2:ENST00000280481.9:c.6020-24322G>A:p.(=)
Pathogenicity Data:
Best Score: 0.398153
REMM: 0.398
Frequency Data:
UK10K: 0.1322%
gnomAD_G_AFR: 0.0410%
gnomAD_G_AMR: 0.1640%
gnomAD_G_NFE: 0.1751%
gnomAD_G_SAS: 0.1249%
INTERGENIC_VARIANT SNV 13-38670004-T-C [0/1] rs571659457
Variant score: 0.311
Transcripts:
FREM2:ENST00000280481.9::
Pathogenicity Data:
Best Score: 0.63004
REMM: 0.630
Frequency Data:
UK10K: 0.0661%
gnomAD_G_AFR: 0.0168%
gnomAD_G_AMR: 0.2221%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.1176%
gnomAD_G_SAS: 1.5554%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 13-38712033-G-A [0/1] rs538700974
Variant score: 0.297
Transcripts:
FREM2:ENST00000280481.9:c.5263+14246G>A:p.(=)
Pathogenicity Data:
Best Score: 0.304135
REMM: 0.304
Frequency Data:
gnomAD_G_AFR: 0.0102%
gnomAD_G_AMR: 0.0421%
gnomAD_G_NFE: 0.0784%
gnomAD_G_SAS: 0.1689%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 13-38810171-G-A [0/1] rs182113092
Variant score: 0.142
Transcripts:
FREM2:ENST00000280481.9:c.6019+25363G>A:p.(=)
Pathogenicity Data:
Best Score: 0.146054
REMM: 0.146
Frequency Data:
UK10K: 0.1058%
gnomAD_G_AFR: 0.0410%
gnomAD_G_AMR: 0.1639%
gnomAD_G_NFE: 0.1796%
gnomAD_G_SAS: 0.1040%
CODING_TRANSCRIPT_INTRON_VARIANT INS 13-38696810-C-CTT [0/1] rs71694503
Variant score: 0.134
Transcripts:
FREM2:ENST00000280481.9:c.5174-888_5174-887insTT:p.(=)
Pathogenicity Data:
Best Score: 0.308427
REMM: 0.308
Frequency Data:
gnomAD_G_AFR: 0.0459%
gnomAD_G_AMR: 0.2931%
gnomAD_G_EAS: 0.1221%
gnomAD_G_NFE: 0.2155%
gnomAD_G_SAS: 1.6459%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 13-38813547-CTCTCTCTCTCTCTCTCTATATA-C [0/1]
Variant score: 0.096
Transcripts:
FREM2:ENST00000280481.9:c.6019+28740_6019+28761del:p.(=)
Pathogenicity Data:
Best Score: 0.096077
REMM: 0.096
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 13-38902691-C-T [0/1] rs182161666
Variant score: 0.046
Transcripts:
FREM2:ENST00000280481.9::
Pathogenicity Data:
Best Score: 0.0460353
REMM: 0.046
Frequency Data:
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0392%
gnomAD_G_NFE: 0.0132%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 13-38813464-TTCTCTCTCTCTCTC-T [0/1] rs1170570605
Variant score: 0.038
Transcripts:
FREM2:ENST00000280481.9:c.6019+28657_6019+28670del:p.(=)
Pathogenicity Data:
Best Score: 0.0674175
REMM: 0.067
Frequency Data:
gnomAD_G_AFR: 1.4306%
gnomAD_G_AMR: 0.0357%
gnomAD_G_EAS: 0.1603%
gnomAD_G_NFE: 0.0126%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 13-38866177-T-C [0|1] rs142000347
Variant score: 0.000
Transcripts:
FREM2:ENST00000280481.9:c.7983+1571T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.4893%
gnomAD_G_AFR: 0.0987%
gnomAD_G_AMR: 0.6933%
gnomAD_G_NFE: 0.8280%
gnomAD_G_SAS: 0.2281%
INTERGENIC_VARIANT SNV 13-38899195-G-A [0/1] rs1407135594
Variant score: 0.000
Transcripts:
FREM2:ENST00000280481.9::
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_NFE: 0.0044%

SPTBN2

Exomiser Score: 0.073 (p=2.9E-1)

Phenotype Score: 0.505

Variant Score: 0.598

Phenotype matches:
Phenotypic similarity 0.264 to mouse mutant involving SPTBN2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002764, short tibia
HP:0006625, Multifocal breast carcinoma - MP:0002764, short tibia
Proximity score 0.505 in interactome to SPTBN1 and phenotypic similarity 0.685 to Developmental delay, impaired speech, and behavioral abnormalities associated with SPTBN1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0032408, Breast mass
HP:0006625, Multifocal breast carcinoma - HP:0032408, Breast mass
Known diseases:
OMIM:600224 Spinocerebellar ataxia 5 - autosomal dominant
OMIM:615386 Spinocerebellar ataxia, autosomal recessive 14 - autosomal recessive
ORPHA:352403 Spectrin-associated autosomal recessive cerebellar ataxia - autosomal recessive
ORPHA:98766 Spinocerebellar ataxia type 5 - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.073 (p=2.9E-1)

Phenotype Score: 0.505

Variant Score: 0.598

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 11-66689815-G-T [0/1] rs750934185
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_MULTIPLE_SUBMITTERS_NO_CONFLICTS)
Variant score: 0.598 CONTRIBUTING VARIANT
Transcripts:
SPTBN2:ENST00000533211.6:c.5939C>A:p.(Ala1980Glu)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_NFE: 0.0012%
gnomAD_E_SAS: 0.0058%
gnomAD_G_NFE: 0.0029%
gnomAD_G_SAS: 0.0207%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.007 (p=5.1E-1)

Phenotype Score: 0.505

Variant Score: 0.338

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 11-66689815-G-T [0/1] rs750934185
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_MULTIPLE_SUBMITTERS_NO_CONFLICTS)
Variant score: 0.598 CONTRIBUTING VARIANT
Transcripts:
SPTBN2:ENST00000533211.6:c.5939C>A:p.(Ala1980Glu)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_NFE: 0.0012%
gnomAD_E_SAS: 0.0058%
gnomAD_G_NFE: 0.0029%
gnomAD_G_SAS: 0.0207%
FIVE_PRIME_UTR_INTRON_VARIANT DEL 11-66722575-CA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.078 CONTRIBUTING VARIANT
Transcripts:
SPTBN2:ENST00000533211.6:c.-113-1136del:p.(=)
Pathogenicity Data:
Best Score: 0.0777317
REMM: 0.078
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 11-66703972-CT-C [0/1] rs11286358
Variant score: 0.015
Transcripts:
SPTBN2:ENST00000533211.6:c.2678+625del:p.(=)
Pathogenicity Data:
Best Score: 0.0151956
REMM: 0.015
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 11-66698060-T-C [0/1] rs1435458916
Variant score: 0.003
Transcripts:
SPTBN2:ENST00000533211.6:c.4014+579A>G:p.(=)
Pathogenicity Data:
Best Score: 0.003425
REMM: 0.003
Frequency Data:
gnomAD_G_NFE: 0.0029%
gnomAD_G_SAS: 0.0207%

NRIP1

Exomiser Score: 0.073 (p=2.9E-1)

Phenotype Score: 0.505

Variant Score: 0.599

Phenotype matches:
Proximity score 0.505 in interactome to NR0B1 and phenotypic similarity 0.614 to 46,XY partial gonadal dysgenesis associated with NR0B1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Proximity score 0.505 in interactome to NR0B1 and phenotypic similarity 0.321 to mouse mutant of NR0B1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0010123, increased bone mineral content
HP:0006625, Multifocal breast carcinoma - MP:0010123, increased bone mineral content
Known diseases:
OMIM:618270 ?Congenital anomalies of kidney and urinary tract 3 (unconfirmed)
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.073 (p=2.9E-1)

Phenotype Score: 0.505

Variant Score: 0.599

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 21-14967577-C-T [0/1] rs141082049
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.599 CONTRIBUTING VARIANT
Transcripts:
NRIP1:ENST00000318948.7:c.616G>A:p.(Val206Met)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 0.0030%
gnomAD_E_AMR: 0.0179%
gnomAD_E_NFE: 0.0052%
gnomAD_E_SAS: 0.0046%
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0131%
gnomAD_G_NFE: 0.0059%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.001 (p=7.7E-1)

Phenotype Score: 0.252

Variant Score: 0.354

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 21-14967577-C-T [0/1] rs141082049
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.599 CONTRIBUTING VARIANT
Transcripts:
NRIP1:ENST00000318948.7:c.616G>A:p.(Val206Met)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 0.0030%
gnomAD_E_AMR: 0.0179%
gnomAD_E_NFE: 0.0052%
gnomAD_E_SAS: 0.0046%
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0131%
gnomAD_G_NFE: 0.0059%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 21-15051090-G-T [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.110 CONTRIBUTING VARIANT
Transcripts:
NRIP1:ENST00000318948.7:c.-537-7516C>A:p.(=)
Pathogenicity Data:
Best Score: 0.110337
REMM: 0.110
Frequency Data:
No frequency data
Other passed variants:
FIVE_PRIME_UTR_INTRON_VARIANT SNV 21-15017003-A-C [0/1] rs532710350
Variant score: 0.003
Transcripts:
NRIP1:ENST00000318948.7:c.-457-2537T>G:p.(=)
Pathogenicity Data:
Best Score: 0.00297222
REMM: 0.003
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AFR: 0.0121%
gnomAD_G_AMR: 0.1308%
gnomAD_G_EAS: 0.0386%
gnomAD_G_NFE: 0.0515%
gnomAD_G_SAS: 0.2698%
FIVE_PRIME_UTR_INTRON_VARIANT SNV 21-15024112-G-A [0/1]
Variant score: 0.000
Transcripts:
NRIP1:ENST00000318948.7:c.-457-9646C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data

TRADD

Exomiser Score: 0.073 (p=2.9E-1)

Phenotype Score: 0.504

Variant Score: 0.599

Phenotype matches:
Proximity score 0.504 in interactome to CASP10 and phenotypic similarity 0.876 to Autoimmune lymphoproliferative syndrome associated with CASP10.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010619, Fibroadenoma of the breast
HP:0006625, Multifocal breast carcinoma - HP:0010619, Fibroadenoma of the breast
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.073 (p=2.9E-1)

Phenotype Score: 0.504

Variant Score: 0.599

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 16-67155435-C-G [0/1] rs200847845
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.599 CONTRIBUTING VARIANT
Transcripts:
TRADD:ENST00000345057.9:c.371G>C:p.(Arg124Pro)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AMR: 0.0022%
gnomAD_E_NFE: 0.0141%
gnomAD_E_SAS: 0.0058%
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0065%
gnomAD_G_NFE: 0.0147%

TMPO

Exomiser Score: 0.072 (p=2.9E-1)

Phenotype Score: 0.502

Variant Score: 0.600

Phenotype matches:
Phenotypic similarity 0.223 to mouse mutant involving TMPO.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0003135, increased erythroid progenitor cell number
HP:0006625, Multifocal breast carcinoma - MP:0003135, increased erythroid progenitor cell number
Proximity score 0.502 in interactome to RNF43 and phenotypic similarity 0.998 to Serrated polyposis syndrome associated with RNF43.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.502 in interactome to RNF43 and phenotypic similarity 0.264 to mouse mutant of RNF43.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002764, short tibia
HP:0006625, Multifocal breast carcinoma - MP:0002764, short tibia
Known diseases:
ORPHA:154 Familial isolated dilated cardiomyopathy - autosomal dominant/recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.072 (p=2.9E-1)

Phenotype Score: 0.502

Variant Score: 0.600

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 12-98531752-C-T [0/1] rs774531403
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_MULTIPLE_SUBMITTERS_NO_CONFLICTS)
Variant score: 0.600 CONTRIBUTING VARIANT
Transcripts:
TMPO:ENST00000556029.6:c.479C>T:p.(Thr160Ile)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_NFE: 0.0002%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.036 (p=3.5E-1)

Phenotype Score: 0.502

Variant Score: 0.519

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 12-98531752-C-T [0/1] rs774531403
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_MULTIPLE_SUBMITTERS_NO_CONFLICTS)
Variant score: 0.600 CONTRIBUTING VARIANT
Transcripts:
TMPO:ENST00000556029.6:c.479C>T:p.(Thr160Ile)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_NFE: 0.0002%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-98520660-G-C [0/1] rs146987808
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.438 CONTRIBUTING VARIANT
Transcripts:
TMPO:ENST00000556029.6:c.279+4514G>C:p.(=)
Pathogenicity Data:
Best Score: 0.446017
REMM: 0.446
Frequency Data:
gnomAD_G_AFR: 0.0025%
gnomAD_G_AMR: 0.1218%
gnomAD_G_NFE: 0.0518%
gnomAD_G_SAS: 0.0846%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-98520276-T-A [0/1]
Variant score: 0.235
Transcripts:
TMPO:ENST00000556029.6:c.279+4130T>A:p.(=)
Pathogenicity Data:
Best Score: 0.234623
REMM: 0.235
Frequency Data:
No frequency data
INTERGENIC_VARIANT INS 12-98555416-C-CTTTTTTTTTTT [0/1] rs770564528
Variant score: 0.178
Transcripts:
TMPO:ENST00000556029.6::
Pathogenicity Data:
Best Score: 0.177679
REMM: 0.178
Frequency Data:
No frequency data
INTERGENIC_VARIANT INS 12-98561377-C-CAAAA [0/1]
Variant score: 0.089
Transcripts:
TMPO:ENST00000556029.6::
Pathogenicity Data:
Best Score: 0.0890472
REMM: 0.089
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 12-98561377-CAAAAAAAAAAAAA-C [0/1]
Variant score: 0.089
Transcripts:
TMPO:ENST00000556029.6::
Pathogenicity Data:
Best Score: 0.0890472
REMM: 0.089
Frequency Data:
No frequency data

TEP1

Exomiser Score: 0.072 (p=2.9E-1)

Phenotype Score: 0.503

Variant Score: 0.599

Phenotype matches:
Proximity score 0.503 in interactome to TERT and phenotypic similarity 0.950 to Familial melanoma associated with TERT.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0100013, Neoplasm of the breast
HP:0006625, Multifocal breast carcinoma - HP:0100013, Neoplasm of the breast
Proximity score 0.503 in interactome to TERT and phenotypic similarity 0.357 to mouse mutant of TERT.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0003345, decreased rib number
HP:0006625, Multifocal breast carcinoma - MP:0003345, decreased rib number
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.072 (p=2.9E-1)

Phenotype Score: 0.503

Variant Score: 0.599

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 14-20373115-C-T [0/1] rs141111607
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.599 CONTRIBUTING VARIANT
Transcripts:
TEP1:ENST00000262715.10:c.6847G>A:p.(Val2283Ile)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 0.0030%
gnomAD_E_AMR: 0.0045%
gnomAD_E_EAS: 0.0076%
gnomAD_E_NFE: 0.0005%
gnomAD_E_SAS: 0.0023%
gnomAD_G_AFR: 0.0072%
gnomAD_G_NFE: 0.0015%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.010 (p=4.7E-1)

Phenotype Score: 0.503

Variant Score: 0.378

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 14-20373115-C-T [0/1] rs141111607
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.599 CONTRIBUTING VARIANT
Transcripts:
TEP1:ENST00000262715.10:c.6847G>A:p.(Val2283Ile)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 0.0030%
gnomAD_E_AMR: 0.0045%
gnomAD_E_EAS: 0.0076%
gnomAD_E_NFE: 0.0005%
gnomAD_E_SAS: 0.0023%
gnomAD_G_AFR: 0.0072%
gnomAD_G_NFE: 0.0015%
FIVE_PRIME_UTR_INTRON_VARIANT DEL 14-20410020-CAAAAAAAAAAAAAAAAAA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.157 CONTRIBUTING VARIANT
Transcripts:
TEP1:ENST00000262715.10:c.-24-1575_-24-1558del:p.(=)
Pathogenicity Data:
Best Score: 0.156991
REMM: 0.157
Frequency Data:
No frequency data
Other passed variants:
SYNONYMOUS_VARIANT SNV 14-20391052-C-G [0/1] rs34817105
Variant score: 0.100
Transcripts:
TEP1:ENST00000262715.10:c.2142G>C:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_EAS: 0.0025%
gnomAD_E_NFE: 0.0001%
gnomAD_E_SAS: 0.0012%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 14-20387677-C-T [0/1] rs370171359
Variant score: 0.004
Transcripts:
TEP1:ENST00000262715.10:c.2684+228G>A:p.(=)
Pathogenicity Data:
Best Score: 0.005
REMM: 0.005
Frequency Data:
UK10K: 0.0926%
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0588%
gnomAD_G_NFE: 0.1102%
gnomAD_G_SAS: 1.0563%
DOWNSTREAM_GENE_VARIANT SNV 14-20362089-C-T [0/1]
Variant score: 0.003
Transcripts:
TEP1:ENST00000262715.10::
Pathogenicity Data:
Best Score: 0.002975
REMM: 0.003
Frequency Data:
No frequency data

IPO4

Exomiser Score: 0.071 (p=2.9E-1)

Phenotype Score: 0.502

Variant Score: 0.599

Phenotype matches:
Proximity score 0.502 in interactome to BAP1 and phenotypic similarity 0.950 to Familial melanoma associated with BAP1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0100013, Neoplasm of the breast
HP:0006625, Multifocal breast carcinoma - HP:0100013, Neoplasm of the breast
Proximity score 0.502 in interactome to BAP1 and phenotypic similarity 0.304 to mouse mutant of BAP1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0003795, abnormal bone structure
HP:0006625, Multifocal breast carcinoma - MP:0003795, abnormal bone structure
Proximity score 0.502 in interactome to BAP1 and phenotypic similarity 0.294 to fish mutant of BAP1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0003356, notochord malformed, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0003356, notochord malformed, abnormal
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.071 (p=2.9E-1)

Phenotype Score: 0.502

Variant Score: 0.599

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 14-24183095-C-T [0/1] rs745476832
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.599 CONTRIBUTING VARIANT
Transcripts:
IPO4:ENST00000354464.11:c.2302G>A:p.(Val768Met)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.0132%
gnomAD_E_AFR: 0.0030%
gnomAD_E_NFE: 0.0020%

ERBB3

Exomiser Score: 0.071 (p=2.9E-1)

Phenotype Score: 0.503

Variant Score: 0.598

Phenotype matches:
Phenotypic similarity 0.230 to zebrafish mutant involving ERBB3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0106560, axon scale decreased amount, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0106560, axon scale decreased amount, abnormal
Proximity score 0.503 in interactome to SOX10 and phenotypic similarity 0.620 to Kallmann syndrome associated with SOX10.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003187, Breast hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0003187, Breast hypoplasia
Proximity score 0.503 in interactome to SOX10 and phenotypic similarity 0.310 to mouse mutant of SOX10.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0004493, dilated cochlea
HP:0006625, Multifocal breast carcinoma - MP:0004493, dilated cochlea
Proximity score 0.503 in interactome to SOX10 and phenotypic similarity 0.300 to fish mutant of SOX10.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0018830, perichondrium disorganized, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0018830, perichondrium disorganized, abnormal
Known diseases:
OMIM:133180 ?Erythroleukemia, familial, susceptibility to (susceptibility)
OMIM:243180 Visceral neuropathy, familial, 1, autosomal recessive - autosomal recessive
OMIM:607598 ?Lethal congenital contractural syndrome 2 (unconfirmed)
ORPHA:388 Hirschsprung disease - autosomal dominant/recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.071 (p=2.9E-1)

Phenotype Score: 0.503

Variant Score: 0.598

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 12-56096813-G-C [0/1] rs760414488
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_MULTIPLE_SUBMITTERS_NO_CONFLICTS)
Variant score: 0.598 CONTRIBUTING VARIANT
Transcripts:
ERBB3:ENST00000267101.8:c.2241G>C:p.(Lys747Asn)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.0264%
gnomAD_E_AFR: 0.0060%
gnomAD_E_AMR: 0.0022%
gnomAD_E_NFE: 0.0059%
gnomAD_E_SAS: 0.0046%
gnomAD_G_NFE: 0.0103%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.025 (p=3.8E-1)

Phenotype Score: 0.503

Variant Score: 0.477

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 12-56096813-G-C [0/1] rs760414488
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_MULTIPLE_SUBMITTERS_NO_CONFLICTS)
Variant score: 0.598 CONTRIBUTING VARIANT
Transcripts:
ERBB3:ENST00000267101.8:c.2241G>C:p.(Lys747Asn)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.0264%
gnomAD_E_AFR: 0.0060%
gnomAD_E_AMR: 0.0022%
gnomAD_E_NFE: 0.0059%
gnomAD_E_SAS: 0.0046%
gnomAD_G_NFE: 0.0103%
UPSTREAM_GENE_VARIANT INS 12-56075857-G-GGATGGGGTGGCTGCCGGGCGGAGACTCTCCTCACTTCCCA [0/1] rs1555210457
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.356 CONTRIBUTING VARIANT
Transcripts:
ERBB3:ENST00000267101.8::
Pathogenicity Data:
Best Score: 0.356021
REMM: 0.356
Frequency Data:
No frequency data
Other passed variants:
UPSTREAM_GENE_VARIANT SNV 12-56075401-C-T [0/1] rs4622308
Variant score: 0.155
Transcripts:
ERBB3:ENST00000267101.8::
Pathogenicity Data:
Best Score: 0.154508
REMM: 0.155
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 12-56068547-CAA-C [0/1]
Variant score: 0.132
Transcripts:
ERBB3:ENST00000267101.8::
Pathogenicity Data:
Best Score: 0.132299
REMM: 0.132
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 12-56068547-CAAA-C [0/1]
Variant score: 0.132
Transcripts:
ERBB3:ENST00000267101.8::
Pathogenicity Data:
Best Score: 0.132299
REMM: 0.132
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-56092389-CA-C [0/1]
Variant score: 0.124
Transcripts:
ERBB3:ENST00000267101.8:c.1110-357del:p.(=)
Pathogenicity Data:
Best Score: 0.124333
REMM: 0.124
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-56092389-CAA-C [0/1]
Variant score: 0.124
Transcripts:
ERBB3:ENST00000267101.8:c.1110-357_1110-356del:p.(=)
Pathogenicity Data:
Best Score: 0.124333
REMM: 0.124
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 12-56068752-CTTT-C [0/1] rs1160014887
Variant score: 0.123
Transcripts:
ERBB3:ENST00000267101.8::
Pathogenicity Data:
Best Score: 0.122999
REMM: 0.123
Frequency Data:
No frequency data

NOD2

Exomiser Score: 0.071 (p=2.9E-1)

Phenotype Score: 0.501

Variant Score: 0.599

Phenotype matches:
Phenotypic similarity 0.237 to mouse mutant involving NOD2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0003436, decreased susceptibility to induced arthritis
HP:0006625, Multifocal breast carcinoma - MP:0003436, decreased susceptibility to induced arthritis
Proximity score 0.501 in interactome to IKBKG and phenotypic similarity 0.619 to Incontinentia pigmenti associated with IKBKG.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0100783, Breast aplasia
HP:0006625, Multifocal breast carcinoma - HP:0100783, Breast aplasia
Proximity score 0.501 in interactome to IKBKG and phenotypic similarity 0.275 to mouse mutant of IKBKG.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002398, abnormal bone marrow cell morphology/development
HP:0006625, Multifocal breast carcinoma - MP:0002398, abnormal bone marrow cell morphology/development
Known diseases:
OMIM:186580 Blau syndrome - autosomal dominant
OMIM:266600 Inflammatory bowel disease 1, Crohn disease (susceptibility)
OMIM:617321 Yao syndrome (susceptibility)
ORPHA:90340 Blau syndrome - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.071 (p=2.9E-1)

Phenotype Score: 0.501

Variant Score: 0.599

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 16-50699898-G-A [0/1] rs139571975
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:2, LB:2, B:1)
Variant score: 0.599 CONTRIBUTING VARIANT
Transcripts:
NOD2:ENST00000647318.2:c.403G>A:p.(Val135Ile)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AMR: 0.0067%
gnomAD_E_EAS: 0.0025%
gnomAD_E_NFE: 0.0094%
gnomAD_G_NFE: 0.0132%

PLA2G4D

Exomiser Score: 0.070 (p=2.9E-1)

Phenotype Score: 0.504

Variant Score: 0.595

Phenotype matches:
Proximity score 0.504 in interactome to PNPLA6 and phenotypic similarity 0.613 to Cerebellar ataxia-hypogonadism syndrome associated with PNPLA6.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.070 (p=2.9E-1)

Phenotype Score: 0.504

Variant Score: 0.595

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 15-42071840-C-T [0/1] rs191357380
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.595 CONTRIBUTING VARIANT
Transcripts:
PLA2G4D:ENST00000290472.4:c.1507G>A:p.(Gly503Ser)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.0529%
gnomAD_E_AFR: 0.0090%
gnomAD_E_AMR: 0.0134%
gnomAD_E_EAS: 0.0076%
gnomAD_E_NFE: 0.0506%
gnomAD_E_SAS: 0.0058%
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0196%
gnomAD_G_NFE: 0.0544%
gnomAD_G_SAS: 0.0207%

HSD17B4

Exomiser Score: 0.070 (p=3.0E-1)

Phenotype Score: 0.535

Variant Score: 0.560

Phenotype matches:
Phenotypic similarity 0.535 to D-bifunctional protein deficiency associated with HSD17B4.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0005257, Thoracic hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0005257, Thoracic hypoplasia
Phenotypic similarity 0.345 to mouse mutant involving HSD17B4.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000157, abnormal sternum morphology
HP:0006625, Multifocal breast carcinoma - MP:0000157, abnormal sternum morphology
Proximity score 0.504 in interactome to HSD17B3 and phenotypic similarity 0.614 to Pseudohermaphroditism, male, with gynecomastia associated with HSD17B3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Known diseases:
OMIM:233400 Perrault syndrome 1 - autosomal recessive
OMIM:261515 D-bifunctional protein deficiency - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.070 (p=3.0E-1)

Phenotype Score: 0.535

Variant Score: 0.560

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.535 to OMIM:261515 D-bifunctional protein deficiency
Variants contributing to score:
MISSENSE_VARIANT SNV 5-119452586-C-G [0/1] rs142889209
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:3, LB:1)
Variant score: 0.596 CONTRIBUTING VARIANT
Transcripts:
HSD17B4:ENST00000510025.7:c.11C>G:p.(Pro4Arg)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 0.0030%
gnomAD_E_AMR: 0.0045%
gnomAD_E_NFE: 0.0332%
gnomAD_E_SAS: 0.0499%
gnomAD_G_NFE: 0.0353%
gnomAD_G_SAS: 0.0414%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-119524300-A-G [0/1] rs911104686
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.524 CONTRIBUTING VARIANT
Transcripts:
HSD17B4:ENST00000510025.7:c.1504-916A>G:p.(=)
Pathogenicity Data:
Best Score: 0.524117
REMM: 0.524
Frequency Data:
gnomAD_G_NFE: 0.0044%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.006 (p=5.4E-1)

Phenotype Score: 0.252

Variant Score: 0.596

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 5-119452586-C-G [0/1] rs142889209
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:3, LB:1)
Variant score: 0.596 CONTRIBUTING VARIANT
Transcripts:
HSD17B4:ENST00000510025.7:c.11C>G:p.(Pro4Arg)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 0.0030%
gnomAD_E_AMR: 0.0045%
gnomAD_E_NFE: 0.0332%
gnomAD_E_SAS: 0.0499%
gnomAD_G_NFE: 0.0353%
gnomAD_G_SAS: 0.0414%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 5-119462248-ATT-A [0/1] rs10524491
Variant score: 0.455
Transcripts:
HSD17B4:ENST00000510025.7:c.112+5881_112+5882del:p.(=)
Pathogenicity Data:
Best Score: 0.454609
REMM: 0.455
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 5-119561909-A-C [0/1] rs577870814
Variant score: 0.380
Transcripts:
HSD17B4:ENST00000510025.7::
Pathogenicity Data:
Best Score: 0.386856
REMM: 0.387
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AFR: 0.0048%
gnomAD_G_NFE: 0.0632%
gnomAD_G_SAS: 0.1242%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-119473264-T-G [0/1]
Variant score: 0.352
Transcripts:
HSD17B4:ENST00000510025.7:c.113-644T>G:p.(=)
Pathogenicity Data:
Best Score: 0.351564
REMM: 0.352
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-119487439-A-G [0/1] rs748472394
Variant score: 0.000
Transcripts:
HSD17B4:ENST00000510025.7:c.623-1753A>G:p.(=)
Pathogenicity Data:
Best Score: 2.85714E-4
REMM: 0.000
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0066%
gnomAD_G_NFE: 0.0412%
gnomAD_G_SAS: 0.0414%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-119492584-G-A [0/1] rs572698768
Variant score: 0.000
Transcripts:
HSD17B4:ENST00000510025.7:c.739+460G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_E_AMR: 0.0536%
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0131%
gnomAD_G_EAS: 0.0386%
gnomAD_G_NFE: 0.0029%

DACT1

Exomiser Score: 0.069 (p=3.0E-1)

Phenotype Score: 0.504

Variant Score: 0.593

Phenotype matches:
Phenotypic similarity 0.471 to Townes-Brocks syndrome associated with DACT1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000772, Abnormal rib morphology
HP:0006625, Multifocal breast carcinoma - HP:0000772, Abnormal rib morphology
Phenotypic similarity 0.360 to mouse mutant involving DACT1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000137, abnormal vertebrae morphology
HP:0006625, Multifocal breast carcinoma - MP:0000137, abnormal vertebrae morphology
Proximity score 0.504 in interactome to APC and phenotypic similarity 0.998 to Gardner syndrome associated with APC.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.504 in interactome to APC and phenotypic similarity 0.315 to mouse mutant of APC.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0004713, split notochord
HP:0006625, Multifocal breast carcinoma - MP:0004713, split notochord
Proximity score 0.504 in interactome to APC and phenotypic similarity 0.228 to fish mutant of APC.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0003761, mandibular arch skeleton immature, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0003761, mandibular arch skeleton immature, abnormal
Known diseases:
OMIM:617466 Townes-Brocks syndrome 2 - autosomal dominant
ORPHA:857 Townes-Brocks syndrome - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.069 (p=3.0E-1)

Phenotype Score: 0.504

Variant Score: 0.593

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.471 to ORPHA:857 Townes-Brocks syndrome
Variants contributing to score:
MISSENSE_VARIANT SNV 14-58638335-C-T [0/1] rs778976254
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.593 CONTRIBUTING VARIANT
Transcripts:
DACT1:ENST00000395153.8:c.133C>T:p.(Arg45Trp)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_NFE: 0.0020%
gnomAD_E_SAS: 0.0267%
gnomAD_G_NFE: 0.0015%
gnomAD_G_SAS: 0.0828%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.004 (p=5.7E-1)

Phenotype Score: 0.252

Variant Score: 0.564

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 14-58638335-C-T [0/1] rs778976254
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.593 CONTRIBUTING VARIANT
Transcripts:
DACT1:ENST00000395153.8:c.133C>T:p.(Arg45Trp)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_NFE: 0.0020%
gnomAD_E_SAS: 0.0267%
gnomAD_G_NFE: 0.0015%
gnomAD_G_SAS: 0.0828%
INTERGENIC_VARIANT DEL 14-58661012-ATTTTTTTTTTTTTTTTT-A [0/1] rs59516157
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.536 CONTRIBUTING VARIANT
Transcripts:
DACT1:ENST00000395153.8::
Pathogenicity Data:
Best Score: 0.535859
REMM: 0.536
Frequency Data:
No frequency data
Other passed variants:
INTERGENIC_VARIANT DEL 14-58661012-ATTTTTTTTTTTTTTTT-A [0/1] rs59516157
Variant score: 0.536
Transcripts:
DACT1:ENST00000395153.8::
Pathogenicity Data:
Best Score: 0.535859
REMM: 0.536
Frequency Data:
No frequency data
DOWNSTREAM_GENE_VARIANT DEL 14-58652796-CCCTT-C [1/1] rs747235627
Variant score: 0.233
Transcripts:
DACT1:ENST00000395153.8::
Pathogenicity Data:
Best Score: 0.232618
REMM: 0.233
Frequency Data:
No frequency data
DOWNSTREAM_GENE_VARIANT INS 14-58650055-C-CT [1/1] rs34550485
Variant score: 0.039
Transcripts:
DACT1:ENST00000395153.8::
Pathogenicity Data:
Best Score: 0.0390802
REMM: 0.039
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 14-58666787-G-T [0/1] rs143240761
Variant score: 0.004
Transcripts:
DACT1:ENST00000395153.8::
Pathogenicity Data:
Best Score: 0.00512143
REMM: 0.005
Frequency Data:
UK10K: 0.3703%
gnomAD_G_AFR: 0.1155%
gnomAD_G_AMR: 0.6404%
gnomAD_G_NFE: 0.4294%
gnomAD_G_SAS: 0.0623%

PNO1

Exomiser Score: 0.068 (p=3.0E-1)

Phenotype Score: 0.501

Variant Score: 0.595

Phenotype matches:
Proximity score 0.501 in interactome to RBM28 and phenotypic similarity 0.614 to ?Alopecia, neurologic defects, and endocrinopathy syndrome associated with RBM28.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.068 (p=3.0E-1)

Phenotype Score: 0.501

Variant Score: 0.595

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 2-68158467-A-G [0/1] rs371420658
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.595 CONTRIBUTING VARIANT
Transcripts:
PNO1:ENST00000263657.7:c.295A>G:p.(Ile99Val)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.0264%
gnomAD_E_AMR: 0.0089%
gnomAD_E_EAS: 0.0630%
gnomAD_E_NFE: 0.0242%
gnomAD_E_SAS: 0.0139%
gnomAD_G_AFR: 0.0072%
gnomAD_G_AMR: 0.0065%
gnomAD_G_EAS: 0.0385%
gnomAD_G_NFE: 0.0147%
gnomAD_G_SAS: 0.0207%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.005 (p=5.5E-1)

Phenotype Score: 0.501

Variant Score: 0.297

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 2-68158467-A-G [0/1] rs371420658
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.595 CONTRIBUTING VARIANT
Transcripts:
PNO1:ENST00000263657.7:c.295A>G:p.(Ile99Val)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.0264%
gnomAD_E_AMR: 0.0089%
gnomAD_E_EAS: 0.0630%
gnomAD_E_NFE: 0.0242%
gnomAD_E_SAS: 0.0139%
gnomAD_G_AFR: 0.0072%
gnomAD_G_AMR: 0.0065%
gnomAD_G_EAS: 0.0385%
gnomAD_G_NFE: 0.0147%
gnomAD_G_SAS: 0.0207%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-68165972-G-C [0/1] rs778976552
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.000 CONTRIBUTING VARIANT
Transcripts:
PNO1:ENST00000263657.7:c.620+3309G>C:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.0264%
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0131%
gnomAD_G_NFE: 0.0118%
gnomAD_G_SAS: 0.0207%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 2-68168921-CT-C [0/1] rs57701897
Variant score: 0.000
Transcripts:
PNO1:ENST00000263657.7:c.621-4425del:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data

SNCA

Exomiser Score: 0.066 (p=3.0E-1)

Phenotype Score: 0.504

Variant Score: 0.588

Phenotype matches:
Proximity score 0.504 in interactome to SPTBN1 and phenotypic similarity 0.685 to Developmental delay, impaired speech, and behavioral abnormalities associated with SPTBN1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0032408, Breast mass
HP:0006625, Multifocal breast carcinoma - HP:0032408, Breast mass
Known diseases:
OMIM:127750 Dementia, Lewy body - autosomal dominant
OMIM:168601 Parkinson disease 1 - autosomal dominant
OMIM:605543 Parkinson disease 4 - autosomal dominant
ORPHA:171695 Parkinsonian-pyramidal syndrome - autosomal dominant
ORPHA:2828 Young-onset Parkinson disease - autosomal recessive
ORPHA:411602 Hereditary late-onset Parkinson disease - autosomal dominant
ORPHA:411602 Hereditary late-onset Parkinson disease - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.066 (p=3.0E-1)

Phenotype Score: 0.504

Variant Score: 0.588

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 4-89821307-A-AAAGGAAGGAAGGGAAG [1|1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.588 CONTRIBUTING VARIANT
Transcripts:
SNCA:ENST00000394991.8:c.306+938_306+939insCTTCCCTTCCTTCCTT:p.(=)
Pathogenicity Data:
Best Score: 0.587859
REMM: 0.588
Frequency Data:
No frequency data

TGFBR1

Exomiser Score: 0.064 (p=3.0E-1)

Phenotype Score: 0.505

Variant Score: 0.583

Phenotype matches:
Phenotypic similarity 0.484 to Familial thoracic aortic aneurysm and aortic dissection associated with TGFBR1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000766, Abnormal sternum morphology
HP:0006625, Multifocal breast carcinoma - HP:0000766, Abnormal sternum morphology
Phenotypic similarity 0.334 to mouse mutant involving TGFBR1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000160, kyphosis
HP:0006625, Multifocal breast carcinoma - MP:0000160, kyphosis
Proximity score 0.505 in interactome to SPTBN1 and phenotypic similarity 0.685 to Developmental delay, impaired speech, and behavioral abnormalities associated with SPTBN1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0032408, Breast mass
HP:0006625, Multifocal breast carcinoma - HP:0032408, Breast mass
Known diseases:
OMIM:132800 Multiple self-healing squamous epithelioma, susceptibility to (susceptibility)
OMIM:609192 Loeys-Dietz syndrome 1 - autosomal dominant
ORPHA:60030 Loeys-Dietz syndrome - autosomal dominant
ORPHA:91387 Familial thoracic aortic aneurysm and aortic dissection - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.064 (p=3.0E-1)

Phenotype Score: 0.505

Variant Score: 0.583

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.484 to ORPHA:91387 Familial thoracic aortic aneurysm and aortic dissection
Phenotypic similarity 0.474 to OMIM:609192 Loeys-Dietz syndrome 1
Phenotypic similarity 0.463 to ORPHA:60030 Loeys-Dietz syndrome
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-99147016-G-A [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.583 CONTRIBUTING VARIANT
Transcripts:
TGFBR1:ENST00000374994.9:c.1255+407G>A:p.(=)
Pathogenicity Data:
Best Score: 0.583229
REMM: 0.583
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.002 (p=6.7E-1)

Phenotype Score: 0.252

Variant Score: 0.465

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 9-99147016-G-A [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.583 CONTRIBUTING VARIANT
Transcripts:
TGFBR1:ENST00000374994.9:c.1255+407G>A:p.(=)
Pathogenicity Data:
Best Score: 0.583229
REMM: 0.583
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT SNV 9-99101813-T-A [0/1] rs183887713
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.347 CONTRIBUTING VARIANT
Transcripts:
TGFBR1:ENST00000374994.9::
Pathogenicity Data:
Best Score: 0.494182
REMM: 0.494
Frequency Data:
UK10K: 0.9918%
gnomAD_G_AFR: 0.1493%
gnomAD_G_AMR: 0.3598%
gnomAD_G_NFE: 0.8543%
gnomAD_G_SAS: 1.1623%
Other passed variants:
INTERGENIC_VARIANT SNV 9-99085949-C-T [0/1] rs945817667
Variant score: 0.008
Transcripts:
TGFBR1:ENST00000374994.9::
Pathogenicity Data:
Best Score: 0.00770556
REMM: 0.008
Frequency Data:
gnomAD_G_AMR: 0.0262%
gnomAD_G_NFE: 0.0059%

IFNAR2

Exomiser Score: 0.057 (p=3.1E-1)

Phenotype Score: 0.502

Variant Score: 0.573

Phenotype matches:
Proximity score 0.502 in interactome to TERT and phenotypic similarity 0.950 to Familial melanoma associated with TERT.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0100013, Neoplasm of the breast
HP:0006625, Multifocal breast carcinoma - HP:0100013, Neoplasm of the breast
Proximity score 0.502 in interactome to TERT and phenotypic similarity 0.357 to mouse mutant of TERT.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0003345, decreased rib number
HP:0006625, Multifocal breast carcinoma - MP:0003345, decreased rib number
Known diseases:
OMIM:616669 Immunodeficiency 45 - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.057 (p=3.1E-1)

Phenotype Score: 0.502

Variant Score: 0.573

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 21-33250270-T-G [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.601 CONTRIBUTING VARIANT
Transcripts:
IFNAR2:ENST00000342136.9:c.540+1416T>G:p.(=)
Pathogenicity Data:
Best Score: 0.600962
REMM: 0.601
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 21-33242783-G-A [0|1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.544 CONTRIBUTING VARIANT
Transcripts:
IFNAR2:ENST00000342136.9:c.55+806G>A:p.(=)
Pathogenicity Data:
Best Score: 0.544413
REMM: 0.544
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.006 (p=5.3E-1)

Phenotype Score: 0.251

Variant Score: 0.601

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 21-33250270-T-G [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.601 CONTRIBUTING VARIANT
Transcripts:
IFNAR2:ENST00000342136.9:c.540+1416T>G:p.(=)
Pathogenicity Data:
Best Score: 0.600962
REMM: 0.601
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT INS 21-33261035-C-CTTTTT [0/1] rs368696822
Variant score: 0.415
Transcripts:
IFNAR2:ENST00000342136.9:c.840+308_840+309insTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.415281
REMM: 0.415
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 21-33261035-CT-C [0/1] rs368696822
Variant score: 0.405
Transcripts:
IFNAR2:ENST00000342136.9:c.840+309del:p.(=)
Pathogenicity Data:
Best Score: 0.415281
REMM: 0.415
Frequency Data:
gnomAD_G_AFR: 0.0569%
gnomAD_G_AMR: 0.0959%
gnomAD_G_EAS: 0.1044%
gnomAD_G_NFE: 0.1679%
gnomAD_G_SAS: 0.0774%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 21-33242758-CGTGTGTGTGTGTGTGTGTGTGTGT-C [0/1]
Variant score: 0.371
Transcripts:
IFNAR2:ENST00000342136.9:c.55+782_55+805del:p.(=)
Pathogenicity Data:
Best Score: 0.371296
REMM: 0.371
Frequency Data:
No frequency data

PEX19

Exomiser Score: 0.052 (p=3.2E-1)

Phenotype Score: 0.514

Variant Score: 0.550

Phenotype matches:
Proximity score 0.514 in interactome to PEX3 and phenotypic similarity 0.643 to ?Peroxisome biogenesis disorder 10B associated with PEX3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Proximity score 0.514 in interactome to PEX3 and phenotypic similarity 0.362 to mouse mutant of PEX3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000137, abnormal vertebrae morphology
HP:0006625, Multifocal breast carcinoma - MP:0000137, abnormal vertebrae morphology
Known diseases:
OMIM:614886 Peroxisome biogenesis disorder 12A (Zellweger) - autosomal recessive
ORPHA:44 Neonatal adrenoleukodystrophy - autosomal recessive
ORPHA:772 Infantile Refsum disease - autosomal recessive
ORPHA:912 Zellweger syndrome - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.052 (p=3.2E-1)

Phenotype Score: 0.514

Variant Score: 0.550

No phenotype matches to diseases with this MOI.
Variants contributing to score:
THREE_PRIME_UTR_EXON_VARIANT SNV 1-160276834-T-C [0/1] rs574056299
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.728 CONTRIBUTING VARIANT
Transcripts:
PEX19:ENST00000368072.10:c.*2717A>G:p.(=)
Pathogenicity Data:
Best Score: 0.735676
REMM: 0.736
Frequency Data:
UK10K: 0.0132%
gnomAD_E_AMR: 0.0770%
gnomAD_E_NFE: 0.0287%
gnomAD_E_SAS: 0.0129%
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0784%
gnomAD_G_NFE: 0.0206%
gnomAD_G_SAS: 0.0207%
DOWNSTREAM_GENE_VARIANT INS 1-160273633-C-CTT [0/1] rs36087426
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.373 CONTRIBUTING VARIANT
Transcripts:
PEX19:ENST00000368072.10::
Pathogenicity Data:
Best Score: 0.385555
REMM: 0.386
Frequency Data:
gnomAD_G_AFR: 0.2226%
gnomAD_G_AMR: 0.0544%
gnomAD_G_EAS: 0.0198%
gnomAD_G_NFE: 0.0329%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.019 (p=4.0E-1)

Phenotype Score: 0.257

Variant Score: 0.728

No phenotype matches to diseases with this MOI.
Variants contributing to score:
THREE_PRIME_UTR_EXON_VARIANT SNV 1-160276834-T-C [0/1] rs574056299
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.728 CONTRIBUTING VARIANT
Transcripts:
PEX19:ENST00000368072.10:c.*2717A>G:p.(=)
Pathogenicity Data:
Best Score: 0.735676
REMM: 0.736
Frequency Data:
UK10K: 0.0132%
gnomAD_E_AMR: 0.0770%
gnomAD_E_NFE: 0.0287%
gnomAD_E_SAS: 0.0129%
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0784%
gnomAD_G_NFE: 0.0206%
gnomAD_G_SAS: 0.0207%

TRPM7

Exomiser Score: 0.052 (p=3.2E-1)

Phenotype Score: 0.505

Variant Score: 0.559

Phenotype matches:
Phenotypic similarity 0.406 to zebrafish mutant involving TRPM7.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0002843, Weberian apparatus malformed, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0002843, Weberian apparatus malformed, abnormal
Proximity score 0.505 in interactome to TRPV6 and phenotypic similarity 0.524 to Neonatal severe primary hyperparathyroidism associated with TRPV6.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000774, Narrow chest
HP:0006625, Multifocal breast carcinoma - HP:0000774, Narrow chest
Proximity score 0.505 in interactome to TRPV6 and phenotypic similarity 0.641 to fish mutant of TRPV6.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0006543, postcranial axial skeleton cartilaginous, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0006543, postcranial axial skeleton cartilaginous, abnormal
Known diseases:
OMIM:105500 Amyotrophic lateral sclerosis-parkinsonism/dementia complex, susceptibility to (susceptibility)
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.052 (p=3.2E-1)

Phenotype Score: 0.505

Variant Score: 0.559

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 15-50682190-A-AAAAAAAAAAAAAAAAAAC [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.559 CONTRIBUTING VARIANT
Transcripts:
TRPM7:ENST00000646667.1:c.3+4340_3+4341insGTTTTTTTTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.558663
REMM: 0.559
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.003 (p=5.9E-1)

Phenotype Score: 0.252

Variant Score: 0.541

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 15-50682190-A-AAAAAAAAAAAAAAAAAAC [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.559 CONTRIBUTING VARIANT
Transcripts:
TRPM7:ENST00000646667.1:c.3+4340_3+4341insGTTTTTTTTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.558663
REMM: 0.559
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 15-50650192-CAAAAAA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.524 CONTRIBUTING VARIANT
Transcripts:
TRPM7:ENST00000646667.1:c.123-1313_123-1308del:p.(=)
Pathogenicity Data:
Best Score: 0.523565
REMM: 0.524
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT INS 15-50638674-T-TTGTATGTATGTATGTA [0/1] rs11283855
Variant score: 0.474
Transcripts:
TRPM7:ENST00000646667.1:c.660+749_660+750insTACATACATACATACA:p.(=)
Pathogenicity Data:
Best Score: 0.473808
REMM: 0.474
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 15-50652328-CAA-C [0/1]
Variant score: 0.405
Transcripts:
TRPM7:ENST00000646667.1:c.123-3445_123-3444del:p.(=)
Pathogenicity Data:
Best Score: 0.404804
REMM: 0.405
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 15-50638358-CAAAAAAAAAAAA-C [0|1]
Variant score: 0.395
Transcripts:
TRPM7:ENST00000646667.1:c.661-777_661-766del:p.(=)
Pathogenicity Data:
Best Score: 0.394795
REMM: 0.395
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 15-50623487-G-GC [0|1]
Variant score: 0.283
Transcripts:
TRPM7:ENST00000646667.1:c.1440+678_1440+679insG:p.(=)
Pathogenicity Data:
Best Score: 0.283185
REMM: 0.283
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 15-50564265-A-AC [1|0]
Variant score: 0.201
Transcripts:
TRPM7:ENST00000646667.1:c.5468-2458_5468-2457insG:p.(=)
Pathogenicity Data:
Best Score: 0.200887
REMM: 0.201
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 15-50564266-A-ATAACATAACATAACATAAC [1|0]
Variant score: 0.198
Transcripts:
TRPM7:ENST00000646667.1:c.5468-2459_5468-2458insGTTATGTTATGTTATGTTA:p.(=)
Pathogenicity Data:
Best Score: 0.198273
REMM: 0.198
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 15-50568078-CA-C [0/1]
Variant score: 0.073
Transcripts:
TRPM7:ENST00000646667.1:c.5467+1808del:p.(=)
Pathogenicity Data:
Best Score: 0.073448
REMM: 0.073
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 15-50654769-G-A [0/1]
Variant score: 0.001
Transcripts:
TRPM7:ENST00000646667.1:c.122+3012C>T:p.(=)
Pathogenicity Data:
Best Score: 5.59524E-4
REMM: 0.001
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 15-50663353-C-T [0/1] rs373367251
Variant score: 0.000
Transcripts:
TRPM7:ENST00000646667.1:c.4-307G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AFR: 0.0024%
gnomAD_G_AMR: 0.0393%
gnomAD_G_NFE: 0.0162%
gnomAD_G_SAS: 0.0414%

ABCC8

Exomiser Score: 0.049 (p=3.3E-1)

Phenotype Score: 0.502

Variant Score: 0.557

Phenotype matches:
Proximity score 0.502 in interactome to FOXA2 and phenotypic similarity 0.676 to Combined pituitary hormone deficiencies, genetic forms associated with FOXA2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
HP:0006625, Multifocal breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
Proximity score 0.502 in interactome to FOXA2 and phenotypic similarity 0.293 to mouse mutant of FOXA2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000932, absent notochord
HP:0006625, Multifocal breast carcinoma - MP:0000932, absent notochord
Known diseases:
OMIM:125853 Diabetes mellitus, noninsulin-dependent - autosomal dominant
OMIM:240800 Hypoglycemia of infancy, leucine-sensitive - autosomal dominant
OMIM:256450 Hyperinsulinemic hypoglycemia, familial, 1 - autosomal dominant/recessive
OMIM:610374 Diabetes mellitus, transient neonatal 2 - autosomal dominant
OMIM:618857 Diabetes mellitus, permanent neonatal 3, with or without neurologic features - autosomal dominant/recessive
ORPHA:276575 Autosomal dominant hyperinsulinism due to SUR1 deficiency - autosomal dominant/recessive
ORPHA:552 MODY - autosomal dominant
ORPHA:79134 DEND syndrome - autosomal dominant/recessive
ORPHA:99885 Isolated permanent neonatal diabetes mellitus - autosomal dominant/recessive
ORPHA:99886 Transient neonatal diabetes mellitus - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.049 (p=3.3E-1)

Phenotype Score: 0.502

Variant Score: 0.557

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 11-17437091-CA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.557 CONTRIBUTING VARIANT
Transcripts:
ABCC8:ENST00000389817.8:c.1631-4848del:p.(=)
Pathogenicity Data:
Best Score: 0.556585
REMM: 0.557
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.029 (p=3.7E-1)

Phenotype Score: 0.502

Variant Score: 0.496

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 11-17437091-CA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.557 CONTRIBUTING VARIANT
Transcripts:
ABCC8:ENST00000389817.8:c.1631-4848del:p.(=)
Pathogenicity Data:
Best Score: 0.556585
REMM: 0.557
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 11-17399275-CAA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.435 CONTRIBUTING VARIANT
Transcripts:
ABCC8:ENST00000389817.8:c.3651-836_3651-835del:p.(=)
Pathogenicity Data:
Best Score: 0.435342
REMM: 0.435
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT INS 11-17450685-C-CTTTTTTT [0/1] rs71047553
Variant score: 0.108
Transcripts:
ABCC8:ENST00000389817.8:c.1177-2015_1177-2014insAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.108117
REMM: 0.108
Frequency Data:
No frequency data

DNM1L

Exomiser Score: 0.049 (p=3.3E-1)

Phenotype Score: 0.502

Variant Score: 0.556

Phenotype matches:
Phenotypic similarity 0.368 to Autosomal dominant optic atrophy, classic form associated with DNM1L.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003691, Scapular winging
HP:0006625, Multifocal breast carcinoma - HP:0003691, Scapular winging
Proximity score 0.502 in interactome to PRKN and phenotypic similarity 0.998 to Ovarian cancer, somatic associated with PRKN.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.502 in interactome to PRKN and phenotypic similarity 0.368 to mouse mutant of PRKN.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000160, kyphosis
HP:0006625, Multifocal breast carcinoma - MP:0000160, kyphosis
Known diseases:
OMIM:610708 Optic atrophy 5 - autosomal dominant
OMIM:614388 Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1 - autosomal dominant/recessive
ORPHA:330050 DNM1L-related encephalopathy due to mitochondrial and peroxisomal fission defect - autosomal dominant/recessive
ORPHA:98673 Autosomal dominant optic atrophy, classic form - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.049 (p=3.3E-1)

Phenotype Score: 0.502

Variant Score: 0.556

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-32738777-T-TAACC [0/1] rs532579256
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.571 CONTRIBUTING VARIANT
Transcripts:
DNM1L:ENST00000549701.6:c.1707+481_1707+482insAACC:p.(=)
DNM1L:ENST00000553257.6:c.1746+481_1746+482insAACC:p.(=)
Pathogenicity Data:
Best Score: 0.672207
REMM: 0.672
Frequency Data:
UK10K: 0.6348%
gnomAD_G_AFR: 0.1394%
gnomAD_G_AMR: 0.4314%
gnomAD_G_NFE: 0.6735%
gnomAD_G_SAS: 0.7457%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-32740684-C-T [0/1] rs142938077
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.540 CONTRIBUTING VARIANT
Transcripts:
DNM1L:ENST00000549701.6:c.1994+166C>T:p.(=)
DNM1L:ENST00000553257.6:c.2033+166C>T:p.(=)
Pathogenicity Data:
Best Score: 0.626621
REMM: 0.627
Frequency Data:
UK10K: 0.6744%
gnomAD_G_AFR: 0.1275%
gnomAD_G_AMR: 0.4182%
gnomAD_G_NFE: 0.6396%
gnomAD_G_SAS: 0.7045%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.000 (p=8.2E-1)

Phenotype Score: 0.502

Variant Score: 0.023

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.368 to ORPHA:98673 Autosomal dominant optic atrophy, classic form
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-32717069-A-G [0/1] rs1268624074
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.023 CONTRIBUTING VARIANT
Transcripts:
DNM1L:ENST00000549701.6:c.620-1574A>G:p.(=)
DNM1L:ENST00000553257.6:c.659-1574A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0233667
REMM: 0.023
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-32703047-C-G [0|1] rs531445737
Variant score: 0.001
Transcripts:
DNM1L:ENST00000549701.6:c.250+1485C>G:p.(=)
DNM1L:ENST00000553257.6:c.250+1485C>G:p.(=)
Pathogenicity Data:
Best Score: 0.001
REMM: 0.001
Frequency Data:
UK10K: 0.5686%
gnomAD_G_AFR: 0.2047%
gnomAD_G_AMR: 0.6698%
gnomAD_G_NFE: 0.9171%
gnomAD_G_SAS: 0.9295%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-32703629-A-G [0/1] rs566286046
Variant score: 0.000
Transcripts:
DNM1L:ENST00000549701.6:c.250+2067A>G:p.(=)
DNM1L:ENST00000553257.6:c.250+2067A>G:p.(=)
Pathogenicity Data:
Best Score: 7.5E-4
REMM: 0.001
Frequency Data:
gnomAD_G_AFR: 0.3084%
gnomAD_G_AMR: 0.7807%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.6531%
gnomAD_G_SAS: 0.1658%

POP1

Exomiser Score: 0.048 (p=3.3E-1)

Phenotype Score: 0.527

Variant Score: 0.526

Phenotype matches:
Phenotypic similarity 0.527 to Anauxetic dysplasia 2 associated with POP1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000914, Shield chest
HP:0006625, Multifocal breast carcinoma - HP:0000914, Shield chest
Proximity score 0.500 in interactome to EIF4A2 and phenotypic similarity 0.643 to Neurodevelopmental disorder with hypotonia and speech delay, with or without seizures associated with EIF4A2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Known diseases:
OMIM:617396 Anauxetic dysplasia 2 - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.048 (p=3.3E-1)

Phenotype Score: 0.527

Variant Score: 0.526

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.527 to OMIM:617396 Anauxetic dysplasia 2
Variants contributing to score:
INTERGENIC_VARIANT SNV 8-98178220-G-A [0/1] rs117824281
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.549 CONTRIBUTING VARIANT
Transcripts:
POP1:ENST00000401707.7::
Pathogenicity Data:
Best Score: 0.791668
REMM: 0.792
Frequency Data:
UK10K: 0.8067%
gnomAD_G_AFR: 0.2141%
gnomAD_G_AMR: 1.1835%
gnomAD_G_NFE: 1.1113%
gnomAD_G_SAS: 0.5390%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-98132906-CA-C [0|1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.503 CONTRIBUTING VARIANT
Transcripts:
POP1:ENST00000401707.7:c.736-1042del:p.(=)
Pathogenicity Data:
Best Score: 0.503316
REMM: 0.503
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.002 (p=6.3E-1)

Phenotype Score: 0.250

Variant Score: 0.503

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-98132906-CA-C [0|1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.503 CONTRIBUTING VARIANT
Transcripts:
POP1:ENST00000401707.7:c.736-1042del:p.(=)
Pathogenicity Data:
Best Score: 0.503316
REMM: 0.503
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT INS 8-98153533-C-CTTTTTTTT [0/1]
Variant score: 0.318
Transcripts:
POP1:ENST00000401707.7:c.2058-2517_2058-2516insTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.318182
REMM: 0.318
Frequency Data:
No frequency data
DOWNSTREAM_GENE_VARIANT DEL 8-98161628-TTCCCCTCCTCTCCCCTCCTC-T [0/1]
Variant score: 0.287
Transcripts:
POP1:ENST00000401707.7::
Pathogenicity Data:
Best Score: 0.287
REMM: 0.287
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 8-98178591-A-G [0/1] rs116852367
Variant score: 0.267
Transcripts:
POP1:ENST00000401707.7::
Pathogenicity Data:
Best Score: 0.784731
REMM: 0.785
Frequency Data:
UK10K: 1.3885%
gnomAD_G_AFR: 0.3187%
gnomAD_G_AMR: 1.6505%
gnomAD_G_NFE: 1.7707%
gnomAD_G_SAS: 0.6878%
FIVE_PRIME_UTR_INTRON_VARIANT INS 8-98121512-G-GT [1/1] rs34259075
Variant score: 0.255
Transcripts:
POP1:ENST00000401707.7:c.-2-1824_-2-1823insT:p.(=)
Pathogenicity Data:
Best Score: 0.254753
REMM: 0.255
Frequency Data:
No frequency data

HNF1A

Exomiser Score: 0.048 (p=3.3E-1)

Phenotype Score: 0.506

Variant Score: 0.549

Phenotype matches:
Phenotypic similarity 0.319 to mouse mutant involving HNF1A.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000063, decreased bone mineral density
HP:0006625, Multifocal breast carcinoma - MP:0000063, decreased bone mineral density
Proximity score 0.506 in interactome to SLC35A2 and phenotypic similarity 0.643 to SLC35A2-CDG associated with SLC35A2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Known diseases:
OMIM:125853 Diabetes mellitus, noninsulin-dependent, 2 (susceptibility)
OMIM:142330 Hepatic adenoma, somatic - autosomal dominant
OMIM:144700 Renal cell carcinoma - unknown
OMIM:222100 Diabetes mellitus, insulin-dependent (susceptibility)
OMIM:600496 MODY, type III - autosomal dominant
OMIM:612520 Diabetes mellitus, insulin-dependent, 20 - unknown
ORPHA:552 MODY - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.048 (p=3.3E-1)

Phenotype Score: 0.506

Variant Score: 0.549

No phenotype matches to diseases with this MOI.
Variants contributing to score:
UPSTREAM_GENE_VARIANT DEL 12-120974787-CTT-C [0/1] rs780861738
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.549 CONTRIBUTING VARIANT
Transcripts:
HNF1A:ENST00000257555.11::
Pathogenicity Data:
Best Score: 0.548746
REMM: 0.549
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.004 (p=5.6E-1)

Phenotype Score: 0.506

Variant Score: 0.284

No phenotype matches to diseases with this MOI.
Variants contributing to score:
UPSTREAM_GENE_VARIANT DEL 12-120974787-CTT-C [0/1] rs780861738
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.549 CONTRIBUTING VARIANT
Transcripts:
HNF1A:ENST00000257555.11::
Pathogenicity Data:
Best Score: 0.548746
REMM: 0.549
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT DEL 12-120975114-CTT-C [0/1] rs1157912239
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.018 CONTRIBUTING VARIANT
Transcripts:
HNF1A:ENST00000257555.11::
Pathogenicity Data:
Best Score: 0.0182687
REMM: 0.018
Frequency Data:
No frequency data
Other passed variants:
UPSTREAM_GENE_VARIANT SNV 12-120974815-G-T [1/1] rs11065377
Variant score: 0.000
Transcripts:
HNF1A:ENST00000257555.11::
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data

CEP164

Exomiser Score: 0.037 (p=3.5E-1)

Phenotype Score: 0.503

Variant Score: 0.523

Phenotype matches:
Proximity score 0.503 in interactome to ALMS1 and phenotypic similarity 0.614 to Alstrom syndrome associated with ALMS1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Known diseases:
OMIM:614845 Nephronophthisis 15 - autosomal recessive
ORPHA:3156 Senior-Loken syndrome - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.037 (p=3.5E-1)

Phenotype Score: 0.503

Variant Score: 0.523

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 11-117389938-CT-C [1/1] rs34794541
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.523 CONTRIBUTING VARIANT
Transcripts:
CEP164:ENST00000278935.8:c.1935-838del:p.(=)
Pathogenicity Data:
Best Score: 0.522969
REMM: 0.523
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.000 (p=9.1E-1)

Phenotype Score: 0.251

Variant Score: 0.063

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 11-117407489-G-A [0/1] rs4938374
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.063 CONTRIBUTING VARIANT
Transcripts:
CEP164:ENST00000278935.8:c.3502-436G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0634234
REMM: 0.063
Frequency Data:
No frequency data
Other passed variants:
MISSENSE_VARIANT SNV 11-117409929-G-A [0/1] rs200520898
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_MULTIPLE_SUBMITTERS_NO_CONFLICTS)
Variant score: 0.589
Transcripts:
CEP164:ENST00000278935.8:c.4060G>A:p.(Asp1354Asn)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.0132%
gnomAD_E_AFR: 0.0030%
gnomAD_E_AMR: 0.0089%
gnomAD_E_NFE: 0.0137%
gnomAD_E_SAS: 0.1310%
gnomAD_G_AFR: 0.0072%
gnomAD_G_AMR: 0.0131%
gnomAD_G_NFE: 0.0279%
gnomAD_G_SAS: 0.1244%
INTERGENIC_VARIANT DEL 11-117322757-ATT-A [1/1] rs34284352
Variant score: 0.043
Transcripts:
CEP164:ENST00000278935.8::
Pathogenicity Data:
Best Score: 0.0430552
REMM: 0.043
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 11-117339522-GTT-G [0/1]
Variant score: 0.032
Transcripts:
CEP164:ENST00000278935.8:c.82+855_82+856del:p.(=)
Pathogenicity Data:
Best Score: 0.0324742
REMM: 0.032
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 11-117407496-G-A [0/1] rs4936373
Variant score: 0.000
Transcripts:
CEP164:ENST00000278935.8:c.3502-429G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
INTERGENIC_VARIANT INS 11-117420892-C-CAAAAA [1/1]
Variant score: 0.000
Transcripts:
CEP164:ENST00000278935.8::
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data

ALDH5A1

Exomiser Score: 0.036 (p=3.5E-1)

Phenotype Score: 0.506

Variant Score: 0.517

Phenotype matches:
Proximity score 0.506 in interactome to IDH1 and phenotypic similarity 0.998 to Maffucci syndrome associated with IDH1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Known diseases:
OMIM:271980 Succinic semialdehyde dehydrogenase deficiency - autosomal recessive
ORPHA:22 Succinic semialdehyde dehydrogenase deficiency - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.036 (p=3.5E-1)

Phenotype Score: 0.506

Variant Score: 0.517

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 6-24520491-G-A [0/1] rs115784602
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:1, LB:5, B:2)
Variant score: 0.528 CONTRIBUTING VARIANT
Transcripts:
ALDH5A1:ENST00000357578.8:c.961G>A:p.(Val321Met)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.6348%
gnomAD_E_AFR: 0.0836%
gnomAD_E_AMR: 0.1409%
gnomAD_E_EAS: 0.0025%
gnomAD_E_NFE: 0.5619%
gnomAD_E_SAS: 0.0812%
gnomAD_G_AFR: 0.0626%
gnomAD_G_AMR: 0.1635%
gnomAD_G_NFE: 0.5748%
gnomAD_G_SAS: 0.0829%
UPSTREAM_GENE_VARIANT DEL 6-24492505-CAA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.506 CONTRIBUTING VARIANT
Transcripts:
ALDH5A1:ENST00000357578.8::
Pathogenicity Data:
Best Score: 0.505833
REMM: 0.506
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.002 (p=6.2E-1)

Phenotype Score: 0.253

Variant Score: 0.506

No phenotype matches to diseases with this MOI.
Variants contributing to score:
UPSTREAM_GENE_VARIANT DEL 6-24492505-CAA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.506 CONTRIBUTING VARIANT
Transcripts:
ALDH5A1:ENST00000357578.8::
Pathogenicity Data:
Best Score: 0.505833
REMM: 0.506
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 6-24506243-CTT-C [0/1]
Variant score: 0.170
Transcripts:
ALDH5A1:ENST00000357578.8:c.726+1259_726+1260del:p.(=)
Pathogenicity Data:
Best Score: 0.169929
REMM: 0.170
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 6-24506273-T-G [0/1] rs2817221
Variant score: 0.000
Transcripts:
ALDH5A1:ENST00000357578.8:c.726+1288T>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data

CDKN2B

Exomiser Score: 0.032 (p=3.6E-1)

Phenotype Score: 0.950

Variant Score: 0.000

Phenotype matches:
Phenotypic similarity 0.950 to Familial melanoma associated with CDKN2B.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0100013, Neoplasm of the breast
HP:0006625, Multifocal breast carcinoma - HP:0100013, Neoplasm of the breast
Proximity score 0.507 in interactome to CDKN2C and phenotypic similarity 0.630 to Multiple endocrine neoplasia type 1 associated with CDKN2C.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0100829, Galactorrhea
HP:0006625, Multifocal breast carcinoma - HP:0100829, Galactorrhea
Proximity score 0.507 in interactome to CDKN2C and phenotypic similarity 0.243 to mouse mutant of CDKN2C.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000321, increased bone marrow cell number
HP:0006625, Multifocal breast carcinoma - MP:0000321, increased bone marrow cell number
Known diseases:
ORPHA:618 Familial melanoma - autosomal dominant
ORPHA:652 Multiple endocrine neoplasia type 1 - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.032 (p=3.6E-1)

Phenotype Score: 0.950

Variant Score: 0.000

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.950 to ORPHA:618 Familial melanoma
Phenotypic similarity 0.630 to ORPHA:652 Multiple endocrine neoplasia type 1
Variants contributing to score:
INTERGENIC_VARIANT SNV 9-22020088-C-T [0/1] rs765313148
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PP4]
Variant score: 0.000 CONTRIBUTING VARIANT
Transcripts:
CDKN2B:ENST00000276925.7::
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
UK10K: 0.0132%
gnomAD_G_AMR: 0.0262%
gnomAD_G_NFE: 0.0088%

SLC2A2

Exomiser Score: 0.030 (p=3.7E-1)

Phenotype Score: 0.502

Variant Score: 0.499

Phenotype matches:
Proximity score 0.502 in interactome to FOXA2 and phenotypic similarity 0.676 to Combined pituitary hormone deficiencies, genetic forms associated with FOXA2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
HP:0006625, Multifocal breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
Proximity score 0.502 in interactome to FOXA2 and phenotypic similarity 0.293 to mouse mutant of FOXA2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000932, absent notochord
HP:0006625, Multifocal breast carcinoma - MP:0000932, absent notochord
Known diseases:
OMIM:125853 Diabetes mellitus, noninsulin-dependent (susceptibility)
OMIM:227810 Fanconi-Bickel syndrome - autosomal recessive
ORPHA:2088 Fanconi-Bickel syndrome - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.030 (p=3.7E-1)

Phenotype Score: 0.502

Variant Score: 0.499

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 3-171009759-T-G [0/1] rs142040797
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.665 CONTRIBUTING VARIANT
Transcripts:
SLC2A2:ENST00000314251.8:c.496+199A>C:p.(=)
Pathogenicity Data:
Best Score: 0.757394
REMM: 0.757
Frequency Data:
UK10K: 0.3306%
gnomAD_G_AFR: 0.0529%
gnomAD_G_AMR: 0.3603%
gnomAD_G_NFE: 0.3912%
gnomAD_G_SAS: 0.6445%
THREE_PRIME_UTR_EXON_VARIANT INS 3-170997894-G-GT [0/1] rs573575421
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.333 CONTRIBUTING VARIANT
Transcripts:
SLC2A2:ENST00000314251.8:c.*8dup:p.(=)
Pathogenicity Data:
Best Score: 0.556028
REMM: 0.556
Frequency Data:
gnomAD_E_AFR: 1.2511%
gnomAD_E_AMR: 0.8841%
gnomAD_E_EAS: 0.2446%
gnomAD_E_NFE: 1.3776%
gnomAD_E_SAS: 1.3166%
gnomAD_G_AFR: 0.4611%
gnomAD_G_AMR: 0.3510%
gnomAD_G_EAS: 0.0589%
gnomAD_G_NFE: 0.4515%
gnomAD_G_SAS: 0.6672%

HAMP

Exomiser Score: 0.028 (p=3.7E-1)

Phenotype Score: 0.503

Variant Score: 0.491

Phenotype matches:
Proximity score 0.503 in interactome to BMP6 and phenotypic similarity 0.614 to Symptomatic form of HFE-related hemochromatosis associated with BMP6.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Proximity score 0.503 in interactome to BMP6 and phenotypic similarity 0.372 to mouse mutant of BMP6.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0004174, abnormal spine curvature
HP:0006625, Multifocal breast carcinoma - MP:0004174, abnormal spine curvature
Known diseases:
OMIM:613313 Hemochromatosis, type 2B - autosomal recessive
ORPHA:79230 HJV or HAMP-related hemochromatosis - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.028 (p=3.7E-1)

Phenotype Score: 0.503

Variant Score: 0.491

No phenotype matches to diseases with this MOI.
Variants contributing to score:
SPLICE_REGION_VARIANT SNV 19-35284855-G-A [0/1] rs201587159
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:1, LB:1)
Variant score: 0.775 CONTRIBUTING VARIANT
Transcripts:
HAMP:ENST00000222304.5:c.150+7G>A:p.?
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.0529%
gnomAD_E_AFR: 0.0060%
gnomAD_E_AMR: 0.0425%
gnomAD_E_EAS: 0.0025%
gnomAD_E_NFE: 0.0720%
gnomAD_E_SAS: 0.1832%
gnomAD_G_AFR: 0.0241%
gnomAD_G_AMR: 0.0981%
gnomAD_G_NFE: 0.0809%
gnomAD_G_SAS: 0.2076%
INTERGENIC_VARIANT SNV 19-35291963-G-C [0/1] rs555354393
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.207 CONTRIBUTING VARIANT
Transcripts:
HAMP:ENST00000222304.5::
Pathogenicity Data:
Best Score: 0.20719
REMM: 0.207
Frequency Data:
gnomAD_G_NFE: 0.0029%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.000 (p=8.7E-1)

Phenotype Score: 0.251

Variant Score: 0.207

No phenotype matches to diseases with this MOI.
Variants contributing to score:
INTERGENIC_VARIANT SNV 19-35291963-G-C [0/1] rs555354393
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.207 CONTRIBUTING VARIANT
Transcripts:
HAMP:ENST00000222304.5::
Pathogenicity Data:
Best Score: 0.20719
REMM: 0.207
Frequency Data:
gnomAD_G_NFE: 0.0029%

PAX6

Exomiser Score: 0.025 (p=3.8E-1)

Phenotype Score: 0.513

Variant Score: 0.469

Phenotype matches:
Phenotypic similarity 0.337 to mouse mutant involving PAX6.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002116, abnormal craniofacial bone morphology
HP:0006625, Multifocal breast carcinoma - MP:0002116, abnormal craniofacial bone morphology
Proximity score 0.513 in interactome to SOX3 and phenotypic similarity 0.676 to Non-acquired panhypopituitarism associated with SOX3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
HP:0006625, Multifocal breast carcinoma - HP:0010311, Aplasia/Hypoplasia of the breasts
Proximity score 0.513 in interactome to SOX3 and phenotypic similarity 0.293 to mouse mutant of SOX3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002100, abnormal tooth morphology
HP:0006625, Multifocal breast carcinoma - MP:0002100, abnormal tooth morphology
Known diseases:
OMIM:106210 Cataract with late-onset corneal dystrophy - autosomal dominant
OMIM:120200 Microphthalmia/coloboma 12 - autosomal dominant
OMIM:120430 ?Coloboma of optic nerve (unconfirmed)
OMIM:136520 Foveal hypoplasia 1 - autosomal dominant
OMIM:148190 Keratitis - autosomal dominant
OMIM:165550 Optic nerve hypoplasia - autosomal dominant
OMIM:604229 Anterior segment dysgenesis 5, multiple subtypes - autosomal dominant
ORPHA:1065 Aniridia-cerebellar ataxia-intellectual disability syndrome - autosomal dominant/recessive
ORPHA:2253 Foveal hypoplasia-presenile cataract syndrome - autosomal dominant
ORPHA:2334 Autosomal dominant keratitis - autosomal dominant
ORPHA:250923 Isolated aniridia - autosomal dominant
ORPHA:35737 Morning glory disc anomaly - autosomal dominant
ORPHA:708 Peters anomaly - autosomal dominant
ORPHA:893 WAGR syndrome (CNV)
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.025 (p=3.8E-1)

Phenotype Score: 0.513

Variant Score: 0.469

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 11-31798832-C-A [0/1] rs529071863
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.874 CONTRIBUTING VARIANT
Transcripts:
PAX6:ENST00000640368.2:c.565+1859G>T:p.(=)
Pathogenicity Data:
Best Score: 0.887007
REMM: 0.887
Frequency Data:
gnomAD_G_AFR: 0.0337%
gnomAD_G_AMR: 0.1045%
gnomAD_G_NFE: 0.0544%
CODING_TRANSCRIPT_INTRON_VARIANT INS 11-31799914-A-AGGGGGGGGGG [0|1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.065 CONTRIBUTING VARIANT
Transcripts:
PAX6:ENST00000640368.2:c.565+776_565+777insCCCCCCCCCC:p.(=)
Pathogenicity Data:
Best Score: 0.06465
REMM: 0.065
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.001 (p=7.7E-1)

Phenotype Score: 0.513

Variant Score: 0.065

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 11-31799914-A-AGGGGGGGGGG [0|1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.065 CONTRIBUTING VARIANT
Transcripts:
PAX6:ENST00000640368.2:c.565+776_565+777insCCCCCCCCCC:p.(=)
Pathogenicity Data:
Best Score: 0.06465
REMM: 0.065
Frequency Data:
No frequency data

OBSL1

Exomiser Score: 0.024 (p=3.9E-1)

Phenotype Score: 0.522

Variant Score: 0.452

Phenotype matches:
Phenotypic similarity 0.522 to 3M syndrome associated with OBSL1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010306, Short thorax
HP:0006625, Multifocal breast carcinoma - HP:0010306, Short thorax
Proximity score 0.500 in interactome to STK11 and phenotypic similarity 0.998 to Peutz-Jeghers syndrome associated with STK11.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.500 in interactome to STK11 and phenotypic similarity 0.306 to mouse mutant of STK11.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002825, abnormal notochord morphology
HP:0006625, Multifocal breast carcinoma - MP:0002825, abnormal notochord morphology
Known diseases:
OMIM:612921 3-M syndrome 2 - autosomal recessive
ORPHA:2616 3M syndrome - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.024 (p=3.9E-1)

Phenotype Score: 0.522

Variant Score: 0.452

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.522 to ORPHA:2616 3M syndrome
Phenotypic similarity 0.517 to OMIM:612921 3-M syndrome 2
Variants contributing to score:
FIVE_PRIME_UTR_EXON_VARIANT INS 2-219571273-C-CG [0|1] rs1437293171
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.550 CONTRIBUTING VARIANT
Transcripts:
OBSL1:ENST00000404537.6:c.-42_-41insC:p.(=)
Pathogenicity Data:
Best Score: 0.555601
REMM: 0.556
Frequency Data:
gnomAD_E_AFR: 0.0053%
gnomAD_E_AMR: 0.0716%
gnomAD_E_EAS: 0.0088%
gnomAD_E_NFE: 0.0398%
gnomAD_E_SAS: 0.0644%
FIVE_PRIME_UTR_EXON_VARIANT SNV 2-219571283-T-G [0|1] rs796511004
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.354 CONTRIBUTING VARIANT
Transcripts:
OBSL1:ENST00000404537.6:c.-51A>C:p.(=)
Pathogenicity Data:
Best Score: 0.35389
REMM: 0.354
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.004 (p=5.8E-1)

Phenotype Score: 0.250

Variant Score: 0.550

No phenotype matches to diseases with this MOI.
Variants contributing to score:
FIVE_PRIME_UTR_EXON_VARIANT INS 2-219571273-C-CG [0|1] rs1437293171
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.550 CONTRIBUTING VARIANT
Transcripts:
OBSL1:ENST00000404537.6:c.-42_-41insC:p.(=)
Pathogenicity Data:
Best Score: 0.555601
REMM: 0.556
Frequency Data:
gnomAD_E_AFR: 0.0053%
gnomAD_E_AMR: 0.0716%
gnomAD_E_EAS: 0.0088%
gnomAD_E_NFE: 0.0398%
gnomAD_E_SAS: 0.0644%

PLA2G3

Exomiser Score: 0.023 (p=3.9E-1)

Phenotype Score: 0.504

Variant Score: 0.469

Phenotype matches:
Proximity score 0.504 in interactome to PNPLA6 and phenotypic similarity 0.613 to Cerebellar ataxia-hypogonadism syndrome associated with PNPLA6.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.023 (p=3.9E-1)

Phenotype Score: 0.504

Variant Score: 0.469

No phenotype matches to diseases with this MOI.
Variants contributing to score:
FRAMESHIFT_VARIANT INS 22-31140148-C-CT [0/1] rs573436695
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.900 CONTRIBUTING VARIANT
Transcripts:
PLA2G3:ENST00000215885.4:c.206dup:p.(Ser70Valfs*3)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.5422%
gnomAD_E_AFR: 0.0747%
gnomAD_E_AMR: 0.4674%
gnomAD_E_NFE: 0.5133%
gnomAD_E_SAS: 0.0684%
gnomAD_G_AFR: 0.0769%
gnomAD_G_AMR: 0.5553%
gnomAD_G_NFE: 0.4719%
gnomAD_G_SAS: 0.0207%
INTERGENIC_VARIANT DEL 22-31152987-TTA-T [0/1] rs1491390910
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.038 CONTRIBUTING VARIANT
Transcripts:
PLA2G3:ENST00000215885.4::
Pathogenicity Data:
Best Score: 0.244141
REMM: 0.244
Frequency Data:
gnomAD_G_AFR: 1.9805%
gnomAD_G_AMR: 0.3715%
gnomAD_G_EAS: 0.1155%
gnomAD_G_NFE: 0.1161%

COG7

Exomiser Score: 0.021 (p=4.0E-1)

Phenotype Score: 0.643

Variant Score: 0.302

Phenotype matches:
Phenotypic similarity 0.643 to Congenital disorder of glycosylation, type IIe associated with COG7.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Proximity score 0.500 in interactome to PMM2 and phenotypic similarity 0.643 to Congenital disorder of glycosylation, type Ia associated with PMM2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Proximity score 0.500 in interactome to PMM2 and phenotypic similarity 0.369 to mouse mutant of PMM2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0004703, abnormal vertebral column morphology
HP:0006625, Multifocal breast carcinoma - MP:0004703, abnormal vertebral column morphology
Proximity score 0.500 in interactome to PMM2 and phenotypic similarity 0.237 to fish mutant of PMM2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0000921, ceratohyal cartilage morphology, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0000921, ceratohyal cartilage morphology, abnormal
Known diseases:
OMIM:608779 Congenital disorder of glycosylation, type IIe - autosomal recessive
ORPHA:79333 COG7-CDG - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.021 (p=4.0E-1)

Phenotype Score: 0.643

Variant Score: 0.302

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.643 to OMIM:608779 Congenital disorder of glycosylation, type IIe
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 16-23408280-C-T [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting, PP4]
Variant score: 0.451 CONTRIBUTING VARIANT
Transcripts:
COG7:ENST00000307149.10:c.1475+2015G>A:p.(=)
Pathogenicity Data:
Best Score: 0.451118
REMM: 0.451
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 16-23424297-CA-C [0/1] rs398042083
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PP4]
Variant score: 0.152 CONTRIBUTING VARIANT
Transcripts:
COG7:ENST00000307149.10:c.1009+451del:p.(=)
Pathogenicity Data:
Best Score: 0.299188
REMM: 0.299
Frequency Data:
gnomAD_G_AFR: 0.4150%
gnomAD_G_AMR: 0.7601%
gnomAD_G_EAS: 0.2927%
gnomAD_G_NFE: 1.5327%
gnomAD_G_SAS: 0.8264%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.001 (p=6.8E-1)

Phenotype Score: 0.250

Variant Score: 0.451

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 16-23408280-C-T [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.451 CONTRIBUTING VARIANT
Transcripts:
COG7:ENST00000307149.10:c.1475+2015G>A:p.(=)
Pathogenicity Data:
Best Score: 0.451118
REMM: 0.451
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 16-23416939-C-A [0/1] rs150124186
ClinVar: LIKELY_BENIGN (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.001
Transcripts:
COG7:ENST00000307149.10:c.1292+28G>T:p.(=)
Pathogenicity Data:
Best Score: 0.00118333
REMM: 0.001
Frequency Data:
UK10K: 1.0182%
gnomAD_E_AFR: 0.2001%
gnomAD_E_AMR: 0.6800%
gnomAD_E_EAS: 0.0025%
gnomAD_E_NFE: 1.1924%
gnomAD_E_SAS: 0.3629%
gnomAD_G_AFR: 0.1684%
gnomAD_G_AMR: 0.9545%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 1.2465%
gnomAD_G_SAS: 0.2279%

TYK2

Exomiser Score: 0.020 (p=4.0E-1)

Phenotype Score: 0.503

Variant Score: 0.456

Phenotype matches:
Phenotypic similarity 0.239 to mouse mutant involving TYK2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0006410, abnormal common myeloid progenitor cell morphology
HP:0006625, Multifocal breast carcinoma - MP:0006410, abnormal common myeloid progenitor cell morphology
Proximity score 0.503 in interactome to FASLG and phenotypic similarity 0.876 to Autoimmune lymphoproliferative syndrome associated with FASLG.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010619, Fibroadenoma of the breast
HP:0006625, Multifocal breast carcinoma - HP:0010619, Fibroadenoma of the breast
Proximity score 0.503 in interactome to FASLG and phenotypic similarity 0.220 to mouse mutant of FASLG.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0001541, abnormal osteoclast physiology
HP:0006625, Multifocal breast carcinoma - MP:0001541, abnormal osteoclast physiology
Proximity score 0.503 in interactome to FASLG and phenotypic similarity 0.300 to fish mutant of FASLG.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0000627, notochord bent, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0000627, notochord bent, abnormal
Known diseases:
OMIM:611521 Immunodeficiency 35 - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.020 (p=4.0E-1)

Phenotype Score: 0.503

Variant Score: 0.456

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 19-10357777-C-T [0/1] rs145437969
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.588 CONTRIBUTING VARIANT
Transcripts:
TYK2:ENST00000525621.6:c.2453G>A:p.(Arg818His)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 0.1407%
gnomAD_E_AMR: 0.0023%
gnomAD_E_EAS: 0.0025%
gnomAD_E_NFE: 0.0033%
gnomAD_G_AFR: 0.1227%
gnomAD_G_AMR: 0.0065%
gnomAD_G_NFE: 0.0029%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 19-10377627-G-A [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.324 CONTRIBUTING VARIANT
Transcripts:
TYK2:ENST00000525621.6:c.193+587C>T:p.(=)
Pathogenicity Data:
Best Score: 0.323669
REMM: 0.324
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.000 (p=8.1E-1)

Phenotype Score: 0.251

Variant Score: 0.324

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 19-10377627-G-A [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.324 CONTRIBUTING VARIANT
Transcripts:
TYK2:ENST00000525621.6:c.193+587C>T:p.(=)
Pathogenicity Data:
Best Score: 0.323669
REMM: 0.324
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 19-10377636-A-G [0/1] rs1436924664
Variant score: 0.291
Transcripts:
TYK2:ENST00000525621.6:c.193+578T>C:p.(=)
Pathogenicity Data:
Best Score: 0.291205
REMM: 0.291
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 19-10377624-A-AGGG [0/1]
Variant score: 0.282
Transcripts:
TYK2:ENST00000525621.6:c.193+589_193+590insCCC:p.(=)
Pathogenicity Data:
Best Score: 0.282024
REMM: 0.282
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 19-10377610-G-A [0/1]
Variant score: 0.278
Transcripts:
TYK2:ENST00000525621.6:c.193+604C>T:p.(=)
Pathogenicity Data:
Best Score: 0.278083
REMM: 0.278
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 19-10377579-G-GATGA [0/1] rs2042186616
Variant score: 0.273
Transcripts:
TYK2:ENST00000525621.6:c.193+634_193+635insTCAT:p.(=)
Pathogenicity Data:
Best Score: 0.273362
REMM: 0.273
Frequency Data:
gnomAD_G_AFR: 0.0044%
gnomAD_G_NFE: 0.0073%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 19-10377659-G-T [0/1]
Variant score: 0.264
Transcripts:
TYK2:ENST00000525621.6:c.193+555C>A:p.(=)
Pathogenicity Data:
Best Score: 0.264265
REMM: 0.264
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 19-10377665-T-TGGATGGATGG [1/1]
Variant score: 0.191
Transcripts:
TYK2:ENST00000525621.6:c.193+548_193+549insCCATCCATCC:p.(=)
Pathogenicity Data:
Best Score: 0.190903
REMM: 0.191
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 19-10377608-G-A [0/1] rs1260886965
Variant score: 0.053
Transcripts:
TYK2:ENST00000525621.6:c.193+606C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0528552
REMM: 0.053
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 19-10377655-A-G [0/1]
Variant score: 0.047
Transcripts:
TYK2:ENST00000525621.6:c.193+559T>C:p.(=)
Pathogenicity Data:
Best Score: 0.046598
REMM: 0.047
Frequency Data:
No frequency data

CDCA8

Exomiser Score: 0.014 (p=4.3E-1)

Phenotype Score: 0.501

Variant Score: 0.419

Phenotype matches:
Proximity score 0.501 in interactome to STAG1 and phenotypic similarity 0.607 to Intellectual developmental disorder, autosomal dominant 47 associated with STAG1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0002558, Supernumerary nipple
HP:0006625, Multifocal breast carcinoma - HP:0002558, Supernumerary nipple
Proximity score 0.501 in interactome to STAG1 and phenotypic similarity 0.368 to mouse mutant of STAG1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000160, kyphosis
HP:0006625, Multifocal breast carcinoma - MP:0000160, kyphosis
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.014 (p=4.3E-1)

Phenotype Score: 0.501

Variant Score: 0.419

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-37704636-CTTT-C [0/1] rs145718694
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.419 CONTRIBUTING VARIANT
Transcripts:
CDCA8:ENST00000373055.6:c.585-804_585-802del:p.(=)
Pathogenicity Data:
Best Score: 0.418758
REMM: 0.419
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.003 (p=6.1E-1)

Phenotype Score: 0.501

Variant Score: 0.238

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-37704636-CTTT-C [0/1] rs145718694
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.419 CONTRIBUTING VARIANT
Transcripts:
CDCA8:ENST00000373055.6:c.585-804_585-802del:p.(=)
Pathogenicity Data:
Best Score: 0.418758
REMM: 0.419
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-37693206-T-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.057 CONTRIBUTING VARIANT
Transcripts:
CDCA8:ENST00000373055.6:c.223+173T>C:p.(=)
Pathogenicity Data:
Best Score: 0.0574476
REMM: 0.057
Frequency Data:
No frequency data

SH3PXD2B

Exomiser Score: 0.014 (p=4.4E-1)

Phenotype Score: 0.614

Variant Score: 0.286

Phenotype matches:
Phenotypic similarity 0.614 to Frank-Ter Haar syndrome associated with SH3PXD2B.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Phenotypic similarity 0.346 to mouse mutant involving SH3PXD2B.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000160, kyphosis
HP:0006625, Multifocal breast carcinoma - MP:0000160, kyphosis
Proximity score 0.501 in interactome to HNRNPK and phenotypic similarity 0.638 to Neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-skeletal anomalies syndrome due to a point mutation associated with HNRNPK.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Known diseases:
OMIM:249420 Frank-ter Haar syndrome - autosomal recessive
ORPHA:137834 Frank-Ter Haar syndrome - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.014 (p=4.4E-1)

Phenotype Score: 0.614

Variant Score: 0.286

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.614 to ORPHA:137834 Frank-Ter Haar syndrome
Phenotypic similarity 0.431 to OMIM:249420 Frank-ter Haar syndrome
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 5-172359387-C-CAAAAAAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting, PP4]
Variant score: 0.432 CONTRIBUTING VARIANT
Transcripts:
SH3PXD2B:ENST00000311601.6:c.563-511_563-510insTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.431531
REMM: 0.432
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 5-172401671-G-A [0/1] rs180929520
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PP4]
Variant score: 0.140 CONTRIBUTING VARIANT
Transcripts:
SH3PXD2B:ENST00000311601.6:c.232+4606C>T:p.(=)
Pathogenicity Data:
Best Score: 0.173748
REMM: 0.174
Frequency Data:
UK10K: 0.6215%
gnomAD_G_AFR: 0.1035%
gnomAD_G_AMR: 0.2549%
gnomAD_G_NFE: 0.8892%
gnomAD_G_SAS: 0.2694%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.001 (p=7.0E-1)

Phenotype Score: 0.250

Variant Score: 0.432

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 5-172359387-C-CAAAAAAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.432 CONTRIBUTING VARIANT
Transcripts:
SH3PXD2B:ENST00000311601.6:c.563-511_563-510insTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.431531
REMM: 0.432
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 5-172416696-CT-C [1/1]
Variant score: 0.010
Transcripts:
SH3PXD2B:ENST00000311601.6:c.156+5719del:p.(=)
Pathogenicity Data:
Best Score: 0.00989405
REMM: 0.010
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 5-172429646-TG-T [0/1]
Variant score: 0.003
Transcripts:
SH3PXD2B:ENST00000311601.6:c.76-7151del:p.(=)
Pathogenicity Data:
Best Score: 0.0028
REMM: 0.003
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT INS 5-172432931-G-GA [0/1]
Variant score: 0.001
Transcripts:
SH3PXD2B:ENST00000311601.6:c.76-10436_76-10435insT:p.(=)
Pathogenicity Data:
Best Score: 0.001
REMM: 0.001
Frequency Data:
No frequency data

CASP1

Exomiser Score: 0.013 (p=4.4E-1)

Phenotype Score: 0.519

Variant Score: 0.388

Phenotype matches:
Proximity score 0.519 in interactome to MEFV and phenotypic similarity 0.998 to Sweet syndrome associated with MEFV.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.519 in interactome to MEFV and phenotypic similarity 0.255 to mouse mutant of MEFV.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002933, joint inflammation
HP:0006625, Multifocal breast carcinoma - MP:0002933, joint inflammation
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.013 (p=4.4E-1)

Phenotype Score: 0.519

Variant Score: 0.388

No phenotype matches to diseases with this MOI.
Variants contributing to score:
UPSTREAM_GENE_VARIANT INS 11-105035618-G-GTTTTTTTTTTTTT [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
ClinVar: UNCERTAIN_SIGNIFICANCE (NO_ASSERTION_CRITERIA_PROVIDED)
Variant score: 0.388 CONTRIBUTING VARIANT
Transcripts:
CASP1:ENST00000533400.6::
Pathogenicity Data:
Best Score: 0.388177
REMM: 0.388
Frequency Data:
No frequency data

NDUFS1

Exomiser Score: 0.012 (p=4.5E-1)

Phenotype Score: 0.503

Variant Score: 0.401

Phenotype matches:
Proximity score 0.503 in interactome to SDHB and phenotypic similarity 0.904 to Cowden syndrome associated with SDHB.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Known diseases:
OMIM:618226 Mitochondrial complex I deficiency, nuclear type 5 - autosomal recessive
ORPHA:2609 Isolated complex I deficiency - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.012 (p=4.5E-1)

Phenotype Score: 0.503

Variant Score: 0.401

No phenotype matches to diseases with this MOI.
Variants contributing to score:
THREE_PRIME_UTR_EXON_VARIANT INS 2-206122629-C-CAAAAAAAAAAAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.490 CONTRIBUTING VARIANT
Transcripts:
NDUFS1:ENST00000233190.11:c.*1544_*1555dup:p.(=)
Pathogenicity Data:
Best Score: 0.490125
REMM: 0.490
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-206134080-A-G [0/1] rs115371115
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.311 CONTRIBUTING VARIANT
Transcripts:
NDUFS1:ENST00000233190.11:c.1393-975T>C:p.(=)
Pathogenicity Data:
Best Score: 0.745003
REMM: 0.745
Frequency Data:
UK10K: 1.6530%
gnomAD_G_AFR: 0.2333%
gnomAD_G_AMR: 0.9146%
gnomAD_G_EAS: 1.0031%
gnomAD_G_NFE: 1.6682%
gnomAD_G_SAS: 1.4493%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.002 (p=6.4E-1)

Phenotype Score: 0.252

Variant Score: 0.490

No phenotype matches to diseases with this MOI.
Variants contributing to score:
THREE_PRIME_UTR_EXON_VARIANT INS 2-206122629-C-CAAAAAAAAAAAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.490 CONTRIBUTING VARIANT
Transcripts:
NDUFS1:ENST00000233190.11:c.*1544_*1555dup:p.(=)
Pathogenicity Data:
Best Score: 0.490125
REMM: 0.490
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 2-206151563-T-G [0/1] rs181429732
Variant score: 0.024
Transcripts:
NDUFS1:ENST00000233190.11:c.153+856A>C:p.(=)
Pathogenicity Data:
Best Score: 0.0253921
REMM: 0.025
Frequency Data:
UK10K: 0.4364%
gnomAD_G_AFR: 0.0192%
gnomAD_G_AMR: 0.0980%
gnomAD_G_NFE: 0.3748%

TNFRSF1B

Exomiser Score: 0.012 (p=4.5E-1)

Phenotype Score: 0.251

Variant Score: 0.685

Phenotype matches:
Proximity score 0.502 in interactome to FASLG and phenotypic similarity 0.876 to Autoimmune lymphoproliferative syndrome associated with FASLG.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0010619, Fibroadenoma of the breast
HP:0006625, Multifocal breast carcinoma - HP:0010619, Fibroadenoma of the breast
Proximity score 0.502 in interactome to FASLG and phenotypic similarity 0.220 to mouse mutant of FASLG.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0001541, abnormal osteoclast physiology
HP:0006625, Multifocal breast carcinoma - MP:0001541, abnormal osteoclast physiology
Proximity score 0.502 in interactome to FASLG and phenotypic similarity 0.300 to fish mutant of FASLG.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0000627, notochord bent, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0000627, notochord bent, abnormal
Known diseases - observed variants incompatible with mode of inheritance:
ORPHA:2584 Classic mycosis fungoides (unconfirmed)
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.012 (p=4.5E-1)

Phenotype Score: 0.251

Variant Score: 0.685

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-12174267-T-TTCTTCTTCTTTTTTA [0/1] rs772504515
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.685 CONTRIBUTING VARIANT
Transcripts:
TNFRSF1B:ENST00000376259.7:c.78+7098_78+7099insTCTTCTTCTTTTTTA:p.(=)
Pathogenicity Data:
Best Score: 0.687444
REMM: 0.687
Frequency Data:
gnomAD_G_AFR: 0.0128%
gnomAD_G_AMR: 0.0068%
gnomAD_G_NFE: 0.0309%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.007 (p=5.0E-1)

Phenotype Score: 0.251

Variant Score: 0.630

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-12174267-T-TTCTTCTTCTTTTTTA [0/1] rs772504515
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.685 CONTRIBUTING VARIANT
Transcripts:
TNFRSF1B:ENST00000376259.7:c.78+7098_78+7099insTCTTCTTCTTTTTTA:p.(=)
Pathogenicity Data:
Best Score: 0.687444
REMM: 0.687
Frequency Data:
gnomAD_G_AFR: 0.0128%
gnomAD_G_AMR: 0.0068%
gnomAD_G_NFE: 0.0309%
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-12196959-C-CT [0/1] rs1173257674
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.575 CONTRIBUTING VARIANT
Transcripts:
TNFRSF1B:ENST00000376259.7:c.900+2341_900+2342insT:p.(=)
Pathogenicity Data:
Best Score: 0.654521
REMM: 0.655
Frequency Data:
gnomAD_G_AFR: 0.6426%
gnomAD_G_AMR: 0.3364%
gnomAD_G_EAS: 0.2420%
gnomAD_G_NFE: 0.2081%
gnomAD_G_SAS: 0.1114%
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-12183699-T-TCTATCTAG [0|1] rs1553163435
Variant score: 0.397
Transcripts:
TNFRSF1B:ENST00000376259.7:c.79-5097_79-5096insCTATCTAG:p.(=)
Pathogenicity Data:
Best Score: 0.41725
REMM: 0.417
Frequency Data:
gnomAD_G_AFR: 0.3038%
gnomAD_G_AMR: 0.0185%
gnomAD_G_EAS: 0.2017%
gnomAD_G_NFE: 0.0548%
gnomAD_G_SAS: 0.1011%
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-12198691-G-GTTTTTTTTTTTT [0/1] rs60313758
Variant score: 0.247
Transcripts:
TNFRSF1B:ENST00000376259.7:c.901-3276_901-3275insTTTTTTTTTTTT:p.(=)
Pathogenicity Data:
Best Score: 0.246956
REMM: 0.247
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT INS 1-12164239-T-TC [0/1] rs35752907
Variant score: 0.004
Transcripts:
TNFRSF1B:ENST00000376259.7::
Pathogenicity Data:
Best Score: 0.0042881
REMM: 0.004
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 1-12203018-A-G [0/1] rs1008892946
Variant score: 0.000
Transcripts:
TNFRSF1B:ENST00000376259.7:c.1105+847A>G:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data

TFAP2B

Exomiser Score: 0.012 (p=4.5E-1)

Phenotype Score: 0.607

Variant Score: 0.281

Phenotype matches:
Phenotypic similarity 0.607 to Char syndrome associated with TFAP2B.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0002558, Supernumerary nipple
HP:0006625, Multifocal breast carcinoma - HP:0002558, Supernumerary nipple
Proximity score 0.528 in interactome to KCTD1 and phenotypic similarity 0.641 to Scalp-ear-nipple syndrome associated with KCTD1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0100783, Breast aplasia
HP:0006625, Multifocal breast carcinoma - HP:0100783, Breast aplasia
Proximity score 0.528 in interactome to KCTD1 and phenotypic similarity 0.319 to mouse mutant of KCTD1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000063, decreased bone mineral density
HP:0006625, Multifocal breast carcinoma - MP:0000063, decreased bone mineral density
Known diseases:
OMIM:169100 Char syndrome - autosomal dominant
OMIM:617035 Patent ductus arteriosus 2 - autosomal dominant
ORPHA:46627 Char syndrome - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.012 (p=4.5E-1)

Phenotype Score: 0.607

Variant Score: 0.281

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.607 to ORPHA:46627 Char syndrome
Variants contributing to score:
INTERGENIC_VARIANT INS 6-50856484-T-TTTTATTTATTTATTTATTTA [0/1] rs58945607
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting, PP4]
Variant score: 0.281 CONTRIBUTING VARIANT
Transcripts:
TFAP2B:ENST00000393655.4::
Pathogenicity Data:
Best Score: 0.281135
REMM: 0.281
Frequency Data:
No frequency data

MMP2

Exomiser Score: 0.011 (p=4.6E-1)

Phenotype Score: 0.502

Variant Score: 0.388

Phenotype matches:
Phenotypic similarity 0.340 to Multicentric osteolysis-nodulosis-arthropathy spectrum associated with MMP2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000916, Broad clavicles
HP:0006625, Multifocal breast carcinoma - HP:0000916, Broad clavicles
Phenotypic similarity 0.329 to mouse mutant involving MMP2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0003795, abnormal bone structure
HP:0006625, Multifocal breast carcinoma - MP:0003795, abnormal bone structure
Phenotypic similarity 0.261 to zebrafish mutant involving MMP2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0001052, mandibular arch skeleton morphology, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0001052, mandibular arch skeleton morphology, abnormal
Proximity score 0.502 in interactome to CDKN2A and phenotypic similarity 0.998 to Familial pancreatic carcinoma associated with CDKN2A.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.502 in interactome to CDKN2A and phenotypic similarity 0.290 to mouse mutant of CDKN2A.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0003789, increased osteosarcoma incidence
HP:0006625, Multifocal breast carcinoma - MP:0003789, increased osteosarcoma incidence
Known diseases:
OMIM:259600 Multicentric osteolysis, nodulosis, and arthropathy - autosomal recessive
ORPHA:371428 Multicentric osteolysis-nodulosis-arthropathy spectrum - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.011 (p=4.6E-1)

Phenotype Score: 0.502

Variant Score: 0.388

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.340 to ORPHA:371428 Multicentric osteolysis-nodulosis-arthropathy spectrum
Variants contributing to score:
MISSENSE_VARIANT SNV 16-55496952-G-C [0/1] rs28730814
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.598 CONTRIBUTING VARIANT
Transcripts:
MMP2:ENST00000219070.9:c.1499G>C:p.(Arg500Pro)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AMR: 0.0268%
gnomAD_E_NFE: 0.0028%
gnomAD_E_SAS: 0.0139%
gnomAD_G_AMR: 0.0262%
gnomAD_G_NFE: 0.0044%
gnomAD_G_SAS: 0.0208%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 16-55504716-G-A [0/1] rs548209272
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.178 CONTRIBUTING VARIANT
Transcripts:
MMP2:ENST00000219070.9:c.1880-623G>A:p.(=)
Pathogenicity Data:
Best Score: 0.180497
REMM: 0.180
Frequency Data:
gnomAD_G_AFR: 0.0494%
gnomAD_G_AMR: 0.0930%
gnomAD_G_NFE: 0.0207%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.006 (p=5.3E-1)

Phenotype Score: 0.251

Variant Score: 0.598

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 16-55496952-G-C [0/1] rs28730814
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.598 CONTRIBUTING VARIANT
Transcripts:
MMP2:ENST00000219070.9:c.1499G>C:p.(Arg500Pro)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AMR: 0.0268%
gnomAD_E_NFE: 0.0028%
gnomAD_E_SAS: 0.0139%
gnomAD_G_AMR: 0.0262%
gnomAD_G_NFE: 0.0044%
gnomAD_G_SAS: 0.0208%
Other passed variants:
INTERGENIC_VARIANT INS 16-55461810-G-GTTTCTTTCTTTCTTTCTTTC [0/1]
Variant score: 0.000
Transcripts:
MMP2:ENST00000219070.9::
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data
INTERGENIC_VARIANT INS 16-55461810-G-GTTTCTTTCTTTCTTTCTTTCTTTCTTTTTTC [0/1]
Variant score: 0.000
Transcripts:
MMP2:ENST00000219070.9::
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
No frequency data

PEX6

Exomiser Score: 0.010 (p=4.7E-1)

Phenotype Score: 0.512

Variant Score: 0.367

Phenotype matches:
Proximity score 0.512 in interactome to PEX3 and phenotypic similarity 0.643 to ?Peroxisome biogenesis disorder 10B associated with PEX3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Proximity score 0.512 in interactome to PEX3 and phenotypic similarity 0.362 to mouse mutant of PEX3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000137, abnormal vertebrae morphology
HP:0006625, Multifocal breast carcinoma - MP:0000137, abnormal vertebrae morphology
Known diseases:
OMIM:614862 Peroxisome biogenesis disorder 4A (Zellweger) - autosomal recessive
OMIM:614863 Peroxisome biogenesis disorder 4B - autosomal dominant/recessive
OMIM:616617 Heimler syndrome 2 - autosomal recessive
ORPHA:3220 Deafness-enamel hypoplasia-nail defects syndrome - autosomal recessive
ORPHA:44 Neonatal adrenoleukodystrophy - autosomal dominant/recessive
ORPHA:772 Infantile Refsum disease - autosomal dominant/recessive
ORPHA:912 Zellweger syndrome - autosomal recessive
ORPHA:95433 Autosomal recessive spinocerebellar ataxia-blindness-deafness syndrome - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.010 (p=4.7E-1)

Phenotype Score: 0.512

Variant Score: 0.367

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 6-42974451-G-GT [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.367 CONTRIBUTING VARIANT
Transcripts:
PEX6:ENST00000304611.13:c.1047-366_1047-365insA:p.(=)
Pathogenicity Data:
Best Score: 0.367103
REMM: 0.367
Frequency Data:
No frequency data

EN2

Exomiser Score: 0.010 (p=4.8E-1)

Phenotype Score: 0.503

Variant Score: 0.373

Phenotype matches:
Proximity score 0.503 in interactome to FGF17 and phenotypic similarity 0.620 to Kallmann syndrome associated with FGF17.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003187, Breast hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0003187, Breast hypoplasia
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.010 (p=4.8E-1)

Phenotype Score: 0.503

Variant Score: 0.373

No phenotype matches to diseases with this MOI.
Variants contributing to score:
INTERGENIC_VARIANT INS 7-155446885-G-GGGAGGGAGGGAGGGAGGGAGGGAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.373 CONTRIBUTING VARIANT
Transcripts:
EN2:ENST00000297375.4::
Pathogenicity Data:
Best Score: 0.372972
REMM: 0.373
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.005 (p=5.4E-1)

Phenotype Score: 0.503

Variant Score: 0.305

No phenotype matches to diseases with this MOI.
Variants contributing to score:
INTERGENIC_VARIANT INS 7-155446885-G-GGGAGGGAGGGAGGGAGGGAGGGAA [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.373 CONTRIBUTING VARIANT
Transcripts:
EN2:ENST00000297375.4::
Pathogenicity Data:
Best Score: 0.372972
REMM: 0.373
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 7-155445662-T-C [0/1] rs72505531
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.238 CONTRIBUTING VARIANT
Transcripts:
EN2:ENST00000297375.4::
Pathogenicity Data:
Best Score: 0.23801
REMM: 0.238
Frequency Data:
No frequency data
Other passed variants:
INTERGENIC_VARIANT SNV 7-155445765-A-G [0/1] rs13236024
Variant score: 0.038
Transcripts:
EN2:ENST00000297375.4::
Pathogenicity Data:
Best Score: 0.0381528
REMM: 0.038
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT SNV 7-155456083-C-T [0/1] rs142525743
Variant score: 0.036
Transcripts:
EN2:ENST00000297375.4::
Pathogenicity Data:
Best Score: 0.0441786
REMM: 0.044
Frequency Data:
UK10K: 0.4099%
gnomAD_G_AFR: 0.0770%
gnomAD_G_AMR: 0.4050%
gnomAD_G_NFE: 0.4365%
gnomAD_G_SAS: 0.8492%

VDR

Exomiser Score: 0.006 (p=5.2E-1)

Phenotype Score: 0.504

Variant Score: 0.325

Phenotype matches:
Phenotypic similarity 0.504 to Hypocalcemic vitamin D-resistant rickets associated with VDR.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000765, Abnormal thorax morphology
HP:0006625, Multifocal breast carcinoma - HP:0000765, Abnormal thorax morphology
Phenotypic similarity 0.325 to mouse mutant involving VDR.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0005605, increased bone mass
HP:0006625, Multifocal breast carcinoma - MP:0005605, increased bone mass
Proximity score 0.504 in interactome to TRPV6 and phenotypic similarity 0.524 to Neonatal severe primary hyperparathyroidism associated with TRPV6.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000774, Narrow chest
HP:0006625, Multifocal breast carcinoma - HP:0000774, Narrow chest
Proximity score 0.504 in interactome to TRPV6 and phenotypic similarity 0.641 to fish mutant of TRPV6.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0006543, postcranial axial skeleton cartilaginous, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0006543, postcranial axial skeleton cartilaginous, abnormal
Known diseases:
OMIM:277440 Rickets, vitamin D-resistant, type IIA - autosomal recessive
ORPHA:93160 Hypocalcemic vitamin D-resistant rickets - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.006 (p=5.2E-1)

Phenotype Score: 0.504

Variant Score: 0.325

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.504 to ORPHA:93160 Hypocalcemic vitamin D-resistant rickets
Phenotypic similarity 0.472 to OMIM:277440 Rickets, vitamin D-resistant, type IIA
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-47848555-CTTTTTT-C [0/1] rs1162881183
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.453 CONTRIBUTING VARIANT
Transcripts:
VDR:ENST00000549336.6:c.756-1753_756-1748del:p.(=)
Pathogenicity Data:
Best Score: 0.453321
REMM: 0.453
Frequency Data:
No frequency data
FIVE_PRIME_UTR_INTRON_VARIANT INS 12-47881119-T-TATATATAC [0/1] rs150135188
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.196 CONTRIBUTING VARIANT
Transcripts:
VDR:ENST00000549336.6:c.-3+1574_-3+1575insGTATATAT:p.(=)
Pathogenicity Data:
Best Score: 0.199476
REMM: 0.199
Frequency Data:
gnomAD_G_AFR: 0.0245%
gnomAD_G_AMR: 0.0667%
gnomAD_G_EAS: 0.0591%
gnomAD_G_NFE: 0.1011%
gnomAD_G_SAS: 0.1051%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.001 (p=6.8E-1)

Phenotype Score: 0.252

Variant Score: 0.453

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 12-47848555-CTTTTTT-C [0/1] rs1162881183
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.453 CONTRIBUTING VARIANT
Transcripts:
VDR:ENST00000549336.6:c.756-1753_756-1748del:p.(=)
Pathogenicity Data:
Best Score: 0.453321
REMM: 0.453
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT INS 12-47871292-C-CTCTTTCTTTCTT [0/1] rs60835997
Variant score: 0.075
Transcripts:
VDR:ENST00000549336.6:c.147-6116_147-6115insAAGAAAGAAAGA:p.(=)
Pathogenicity Data:
Best Score: 0.0753131
REMM: 0.075
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-47872300-G-A [0/1] rs188453629
Variant score: 0.065
Transcripts:
VDR:ENST00000549336.6:c.146+6668C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0828401
REMM: 0.083
Frequency Data:
UK10K: 0.3438%
gnomAD_G_AFR: 0.0986%
gnomAD_G_AMR: 0.9413%
gnomAD_G_NFE: 0.5042%
gnomAD_G_SAS: 0.2897%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 12-47853209-G-A [0/1] rs1002164523
Variant score: 0.000
Transcripts:
VDR:ENST00000549336.6:c.755+2421C>T:p.(=)
Pathogenicity Data:
Best Score: 0.0
REMM: 0.000
Frequency Data:
gnomAD_G_AFR: 0.0290%
gnomAD_G_EAS: 0.0193%
gnomAD_G_NFE: 0.0191%

PEX1

Exomiser Score: 0.006 (p=5.2E-1)

Phenotype Score: 0.251

Variant Score: 0.609

Phenotype matches:
Phenotypic similarity 0.477 to Peroxisome biogenesis disorder 1A (Zellweger) associated with PEX1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0001591, Bell-shaped thorax
HP:0006625, Multifocal breast carcinoma - HP:0001591, Bell-shaped thorax
Proximity score 0.502 in interactome to PEX3 and phenotypic similarity 0.643 to ?Peroxisome biogenesis disorder 10B associated with PEX3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Proximity score 0.502 in interactome to PEX3 and phenotypic similarity 0.362 to mouse mutant of PEX3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000137, abnormal vertebrae morphology
HP:0006625, Multifocal breast carcinoma - MP:0000137, abnormal vertebrae morphology
Known diseases:
OMIM:214100 Peroxisome biogenesis disorder 1A (Zellweger) - autosomal recessive
OMIM:234580 Heimler syndrome 1 - autosomal recessive
OMIM:601539 Peroxisome biogenesis disorder 1B (NALD/IRD) - autosomal recessive
ORPHA:3220 Deafness-enamel hypoplasia-nail defects syndrome - autosomal recessive
ORPHA:44 Neonatal adrenoleukodystrophy - autosomal recessive
ORPHA:772 Infantile Refsum disease - autosomal recessive
ORPHA:912 Zellweger syndrome - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.006 (p=5.2E-1)

Phenotype Score: 0.251

Variant Score: 0.609

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 7-92490632-CAAAAAAAAAAA-C [0/1] rs35917694
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.609 CONTRIBUTING VARIANT
Transcripts:
PEX1:ENST00000248633.9:c.3438+629_3438+639del:p.(=)
Pathogenicity Data:
Best Score: 0.609521
REMM: 0.610
Frequency Data:
gnomAD_G_NFE: 0.0049%

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.000 (p=8.4E-1)

Phenotype Score: 0.502

Variant Score: 0.004

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.477 to OMIM:214100 Peroxisome biogenesis disorder 1A (Zellweger)
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 7-92516055-A-AG [1/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.004 CONTRIBUTING VARIANT
Transcripts:
PEX1:ENST00000248633.9:c.1239+1220_1239+1221insC:p.(=)
Pathogenicity Data:
Best Score: 0.00421429
REMM: 0.004
Frequency Data:
No frequency data

PTGER1

Exomiser Score: 0.006 (p=5.2E-1)

Phenotype Score: 0.501

Variant Score: 0.325

Phenotype matches:
Phenotypic similarity 0.199 to mouse mutant involving PTGER1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0008080, abnormal CD8-positive, alpha-beta T cell differentiation
HP:0006625, Multifocal breast carcinoma - MP:0008080, abnormal CD8-positive, alpha-beta T cell differentiation
Proximity score 0.501 in interactome to GNAS and phenotypic similarity 0.998 to McCune-Albright syndrome associated with GNAS.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.501 in interactome to GNAS and phenotypic similarity 0.322 to mouse mutant of GNAS.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0014167, ectopic bone
HP:0006625, Multifocal breast carcinoma - MP:0014167, ectopic bone
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.006 (p=5.2E-1)

Phenotype Score: 0.501

Variant Score: 0.325

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 19-14474073-G-T [0/1] rs201044848
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.565 CONTRIBUTING VARIANT
Transcripts:
PTGER1:ENST00000292513.4:c.248C>A:p.(Thr83Asn)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 0.0517%
gnomAD_E_AMR: 0.0351%
gnomAD_E_NFE: 0.3572%
gnomAD_E_SAS: 0.0745%
gnomAD_G_AFR: 0.0604%
gnomAD_G_AMR: 0.0789%
gnomAD_G_NFE: 0.3144%
gnomAD_G_SAS: 0.0622%
UPSTREAM_GENE_VARIANT SNV 19-14476509-C-T [0/1] rs151218465
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.085 CONTRIBUTING VARIANT
Transcripts:
PTGER1:ENST00000292513.4::
Pathogenicity Data:
Best Score: 0.106225
REMM: 0.106
Frequency Data:
UK10K: 0.7273%
gnomAD_G_AFR: 0.1515%
gnomAD_G_AMR: 0.3303%
gnomAD_G_NFE: 0.9046%
gnomAD_G_SAS: 0.7705%

TPM3

Exomiser Score: 0.006 (p=5.2E-1)

Phenotype Score: 0.506

Variant Score: 0.320

Phenotype matches:
Phenotypic similarity 0.504 to Intermediate nemaline myopathy associated with TPM3.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000765, Abnormal thorax morphology
HP:0006625, Multifocal breast carcinoma - HP:0000765, Abnormal thorax morphology
Proximity score 0.506 in interactome to DES and phenotypic similarity 0.614 to Scapuloperoneal syndrome, neurogenic, Kaeser type associated with DES.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Known diseases:
OMIM:255310 Congenital myopathy 4A, autosomal dominant - autosomal dominant/recessive
OMIM:609284 Congenital myopathy 4B, autosomal recessive - autosomal dominant/recessive
ORPHA:171433 Intermediate nemaline myopathy - autosomal dominant/recessive
ORPHA:171439 Childhood-onset nemaline myopathy - autosomal dominant/recessive
ORPHA:171881 Cap myopathy - autosomal dominant/recessive
ORPHA:2020 Congenital fiber-type disproportion myopathy - autosomal dominant/recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.006 (p=5.2E-1)

Phenotype Score: 0.506

Variant Score: 0.320

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.504 to ORPHA:171433 Intermediate nemaline myopathy
Phenotypic similarity 0.504 to ORPHA:171439 Childhood-onset nemaline myopathy
Phenotypic similarity 0.458 to ORPHA:171881 Cap myopathy
Phenotypic similarity 0.444 to OMIM:609284 Congenital myopathy 4B, autosomal recessive
Phenotypic similarity 0.439 to ORPHA:2020 Congenital fiber-type disproportion myopathy
Variants contributing to score:
THREE_PRIME_UTR_EXON_VARIANT DEL 1-154166465-GC-G [0/1] rs563553310
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.608 CONTRIBUTING VARIANT
Transcripts:
TPM3:ENST00000651641.1:c.*1471del:p.(=)
Pathogenicity Data:
Best Score: 0.679242
REMM: 0.679
Frequency Data:
UK10K: 0.4099%
gnomAD_E_AFR: 0.1546%
gnomAD_E_AMR: 0.3016%
gnomAD_E_NFE: 0.5625%
gnomAD_E_SAS: 0.1023%
gnomAD_G_AFR: 0.1035%
gnomAD_G_AMR: 0.3335%
gnomAD_G_NFE: 0.5719%
gnomAD_G_SAS: 0.1036%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 1-154174368-GTATATATA-G [0/1] rs34224787
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.031 CONTRIBUTING VARIANT
Transcripts:
TPM3:ENST00000651641.1:c.378-1175_378-1168del:p.(=)
Pathogenicity Data:
Best Score: 0.0961972
REMM: 0.096
Frequency Data:
gnomAD_G_AFR: 1.1852%
gnomAD_G_AMR: 1.5677%
gnomAD_G_EAS: 1.1166%
gnomAD_G_NFE: 1.6758%
gnomAD_G_SAS: 1.7958%

GATA4

Exomiser Score: 0.006 (p=5.3E-1)

Phenotype Score: 0.255

Variant Score: 0.598

Phenotype matches:
Phenotypic similarity 0.614 to 46,XY partial gonadal dysgenesis associated with GATA4.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Phenotypic similarity 0.267 to mouse mutant involving GATA4.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0012061, abnormal diaphragm central tendon morphology
HP:0006625, Multifocal breast carcinoma - MP:0012061, abnormal diaphragm central tendon morphology
Proximity score 0.510 in interactome to ZFPM2 and phenotypic similarity 0.614 to 46,XY partial gonadal dysgenesis associated with ZFPM2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Known diseases:
OMIM:187500 Tetralogy of Fallot - autosomal dominant
OMIM:607941 Atrial septal defect 2 - autosomal dominant
OMIM:614429 Ventricular septal defect 1 - autosomal dominant
OMIM:614430 Atrioventricular septal defect 4 - autosomal dominant
OMIM:615542 ?Testicular anomalies with or without congenital heart disease (unconfirmed)
ORPHA:251510 46,XY partial gonadal dysgenesis - autosomal dominant
ORPHA:3303 Tetralogy of Fallot - autosomal dominant
ORPHA:334 Familial atrial fibrillation - autosomal dominant
ORPHA:99103 Atrial septal defect, ostium secundum type - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.006 (p=5.3E-1)

Phenotype Score: 0.255

Variant Score: 0.598

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-11711747-CA-C [1/1] rs71205018
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.598 CONTRIBUTING VARIANT
Transcripts:
GATA4:ENST00000532059.6:c.616+2820del:p.(=)
Pathogenicity Data:
Best Score: 0.598125
REMM: 0.598
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.001 (p=7.2E-1)

Phenotype Score: 0.614

Variant Score: 0.004

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.614 to ORPHA:251510 46,XY partial gonadal dysgenesis
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 8-11716014-T-C [0/1] rs1193857228
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PP4]
Variant score: 0.004 CONTRIBUTING VARIANT
Transcripts:
GATA4:ENST00000532059.6:c.616+7086T>C:p.(=)
Pathogenicity Data:
Best Score: 0.00361111
REMM: 0.004
Frequency Data:
gnomAD_G_SAS: 0.0207%
Other passed variants:
INTERGENIC_VARIANT SNV 8-11698744-C-T [0/1] rs560367799
Variant score: 0.852
Transcripts:
GATA4:ENST00000532059.6::
Pathogenicity Data:
Best Score: 0.876223
REMM: 0.876
Frequency Data:
UK10K: 0.0661%
gnomAD_G_AFR: 0.0385%
gnomAD_G_AMR: 0.1829%
gnomAD_G_NFE: 0.0838%
gnomAD_G_SAS: 0.0415%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 8-11710688-CA-C [1/1]
Variant score: 0.390
Transcripts:
GATA4:ENST00000532059.6:c.616+1761del:p.(=)
Pathogenicity Data:
Best Score: 0.390416
REMM: 0.390
Frequency Data:
No frequency data
INTERGENIC_VARIANT INS 8-11769396-C-CA [0/1] rs983311371
Variant score: 0.238
Transcripts:
GATA4:ENST00000532059.6::
Pathogenicity Data:
Best Score: 0.244602
REMM: 0.245
Frequency Data:
gnomAD_G_AFR: 0.0503%
gnomAD_G_AMR: 0.1914%
gnomAD_G_NFE: 0.1115%
gnomAD_G_SAS: 0.0874%

MMP1

Exomiser Score: 0.005 (p=5.4E-1)

Phenotype Score: 0.501

Variant Score: 0.311

Phenotype matches:
Proximity score 0.501 in interactome to SNAI1 and phenotypic similarity 0.641 to fish mutant of SNAI1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0010249, postcranial axial skeleton ossified, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0010249, postcranial axial skeleton ossified, abnormal
Known diseases:
OMIM:226600 Epidermolysis bullosa dystrophica, autosomal recessive, modifier of (susceptibility)
OMIM:606963 COPD, rate of decline of lung function in - unknown
ORPHA:79408 Autosomal recessive generalized dystrophic epidermolysis bullosa, severe form (unconfirmed)
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.005 (p=5.4E-1)

Phenotype Score: 0.501

Variant Score: 0.311

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 11-102792725-T-C [0/1] rs56028730
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.592 CONTRIBUTING VARIANT
Transcripts:
MMP1:ENST00000315274.7:c.913A>G:p.(Thr305Ala)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.0926%
gnomAD_E_AFR: 0.0239%
gnomAD_E_AMR: 0.0112%
gnomAD_E_NFE: 0.0675%
gnomAD_E_SAS: 0.0081%
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0132%
gnomAD_G_NFE: 0.0752%
gnomAD_G_SAS: 0.0210%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 11-102796966-C-T [0/1] rs144507775
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.030 CONTRIBUTING VARIANT
Transcripts:
MMP1:ENST00000315274.7:c.499+48G>A:p.(=)
Pathogenicity Data:
Best Score: 0.0319925
REMM: 0.032
Frequency Data:
gnomAD_E_AFR: 0.3967%
gnomAD_E_AMR: 0.0255%
gnomAD_E_EAS: 0.0026%
gnomAD_E_NFE: 0.0034%
gnomAD_E_SAS: 0.0037%
gnomAD_G_AFR: 0.4287%
gnomAD_G_AMR: 0.0850%
gnomAD_G_NFE: 0.0074%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.005 (p=5.4E-1)

Phenotype Score: 0.251

Variant Score: 0.592

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 11-102792725-T-C [0/1] rs56028730
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: UNCERTAIN_SIGNIFICANCE (CRITERIA_PROVIDED_SINGLE_SUBMITTER)
Variant score: 0.592 CONTRIBUTING VARIANT
Transcripts:
MMP1:ENST00000315274.7:c.913A>G:p.(Thr305Ala)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.0926%
gnomAD_E_AFR: 0.0239%
gnomAD_E_AMR: 0.0112%
gnomAD_E_NFE: 0.0675%
gnomAD_E_SAS: 0.0081%
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0132%
gnomAD_G_NFE: 0.0752%
gnomAD_G_SAS: 0.0210%

VHL

Exomiser Score: 0.005 (p=5.4E-1)

Phenotype Score: 0.503

Variant Score: 0.303

Phenotype matches:
Phenotypic similarity 0.251 to mouse mutant involving VHL.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0008254, increased megakaryocyte cell number
HP:0006625, Multifocal breast carcinoma - MP:0008254, increased megakaryocyte cell number
Proximity score 0.503 in interactome to PRKN and phenotypic similarity 0.998 to Ovarian cancer, somatic associated with PRKN.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.503 in interactome to PRKN and phenotypic similarity 0.368 to mouse mutant of PRKN.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000160, kyphosis
HP:0006625, Multifocal breast carcinoma - MP:0000160, kyphosis
Known diseases:
OMIM:144700 Renal cell carcinoma, somatic - unknown
OMIM:171300 Pheochromocytoma - autosomal dominant
OMIM:193300 von Hippel-Lindau syndrome - autosomal dominant
OMIM:263400 Erythrocytosis, familial, 2 - autosomal recessive
ORPHA:29072 Hereditary pheochromocytoma-paraganglioma - autosomal dominant
ORPHA:892 Von Hippel-Lindau disease - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.005 (p=5.4E-1)

Phenotype Score: 0.503

Variant Score: 0.303

No phenotype matches to diseases with this MOI.
Variants contributing to score:
THREE_PRIME_UTR_EXON_VARIANT DEL 3-10152481-CTT-C [1/1] rs71052299
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.303 CONTRIBUTING VARIANT
Transcripts:
VHL:ENST00000256474.3:c.*2544_*2545del:p.(=)
Pathogenicity Data:
Best Score: 0.303312
REMM: 0.303
Frequency Data:
No frequency data

CBLC

Exomiser Score: 0.004 (p=5.6E-1)

Phenotype Score: 0.502

Variant Score: 0.289

Phenotype matches:
Proximity score 0.502 in interactome to FGFR2 and phenotypic similarity 0.998 to Saethre-Chotzen syndrome associated with FGFR2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.502 in interactome to FGFR2 and phenotypic similarity 0.360 to mouse mutant of FGFR2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002114, abnormal axial skeleton morphology
HP:0006625, Multifocal breast carcinoma - MP:0002114, abnormal axial skeleton morphology
No known disease
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.004 (p=5.6E-1)

Phenotype Score: 0.502

Variant Score: 0.289

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 19-44792407-A-G [0/1] rs149074838
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.348 CONTRIBUTING VARIANT
Transcripts:
CBLC:ENST00000647358.2:c.1030A>G:p.(Met344Val)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.8596%
gnomAD_E_AFR: 0.1255%
gnomAD_E_AMR: 0.3421%
gnomAD_E_NFE: 0.8890%
gnomAD_E_SAS: 1.3021%
gnomAD_G_AFR: 0.1613%
gnomAD_G_AMR: 0.3274%
gnomAD_G_EAS: 0.0194%
gnomAD_G_NFE: 0.9028%
gnomAD_G_SAS: 1.4114%
CODING_TRANSCRIPT_INTRON_VARIANT DEL 19-44791133-AAAAG-A [0/1] rs550167833
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.231 CONTRIBUTING VARIANT
Transcripts:
CBLC:ENST00000647358.2:c.1005+1043_1005+1046del:p.(=)
Pathogenicity Data:
Best Score: 0.268705
REMM: 0.269
Frequency Data:
gnomAD_G_AFR: 0.0121%
gnomAD_G_AMR: 0.0197%
gnomAD_G_EAS: 0.7176%
gnomAD_G_NFE: 0.0118%
gnomAD_G_SAS: 0.0208%
Other passed variants:
DOWNSTREAM_GENE_VARIANT SNV 19-44801819-T-G [0/1] rs1303839807
Variant score: 0.104
Transcripts:
CBLC:ENST00000647358.2::
Pathogenicity Data:
Best Score: 0.15924
REMM: 0.159
Frequency Data:
gnomAD_G_AFR: 1.0904%
gnomAD_G_AMR: 1.2733%
gnomAD_G_EAS: 1.2667%
gnomAD_G_NFE: 0.9839%
gnomAD_G_SAS: 1.1285%

ESCO2

Exomiser Score: 0.004 (p=5.6E-1)

Phenotype Score: 0.501

Variant Score: 0.286

Phenotype matches:
Phenotypic similarity 0.471 to Juberg-Hayward syndrome associated with ESCO2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000772, Abnormal rib morphology
HP:0006625, Multifocal breast carcinoma - HP:0000772, Abnormal rib morphology
Phenotypic similarity 0.244 to zebrafish mutant involving ESCO2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0001147, mandibular arch skeleton aplastic, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0001147, mandibular arch skeleton aplastic, abnormal
Proximity score 0.501 in interactome to STAG1 and phenotypic similarity 0.607 to Intellectual developmental disorder, autosomal dominant 47 associated with STAG1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0002558, Supernumerary nipple
HP:0006625, Multifocal breast carcinoma - HP:0002558, Supernumerary nipple
Proximity score 0.501 in interactome to STAG1 and phenotypic similarity 0.368 to mouse mutant of STAG1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000160, kyphosis
HP:0006625, Multifocal breast carcinoma - MP:0000160, kyphosis
Known diseases:
OMIM:216100 Juberg-Hayward syndrome - autosomal recessive
OMIM:268300 Roberts-SC phocomelia syndrome - autosomal recessive
ORPHA:2319 Juberg-Hayward syndrome - autosomal recessive
ORPHA:3103 Roberts syndrome - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.004 (p=5.6E-1)

Phenotype Score: 0.501

Variant Score: 0.286

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.471 to ORPHA:2319 Juberg-Hayward syndrome
Variants contributing to score:
THREE_PRIME_UTR_EXON_VARIANT DEL 8-27805287-CAAAAAAAAAAA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.306 CONTRIBUTING VARIANT
Transcripts:
ESCO2:ENST00000305188.13:c.*1868_*1878del:p.(=)
Pathogenicity Data:
Best Score: 0.305988
REMM: 0.306
Frequency Data:
No frequency data
THREE_PRIME_UTR_EXON_VARIANT DEL 8-27805287-CAAAA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.266 CONTRIBUTING VARIANT
Transcripts:
ESCO2:ENST00000305188.13:c.*1875_*1878del:p.(=)
Pathogenicity Data:
Best Score: 0.265707
REMM: 0.266
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.000 (p=8.2E-1)

Phenotype Score: 0.251

Variant Score: 0.306

No phenotype matches to diseases with this MOI.
Variants contributing to score:
THREE_PRIME_UTR_EXON_VARIANT DEL 8-27805287-CAAAAAAAAAAA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.306 CONTRIBUTING VARIANT
Transcripts:
ESCO2:ENST00000305188.13:c.*1868_*1878del:p.(=)
Pathogenicity Data:
Best Score: 0.305988
REMM: 0.306
Frequency Data:
No frequency data

RAB33B

Exomiser Score: 0.003 (p=5.9E-1)

Phenotype Score: 0.532

Variant Score: 0.224

Phenotype matches:
Phenotypic similarity 0.532 to Smith-McCort dysplasia 2 associated with RAB33B.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0001552, Barrel-shaped chest
HP:0006625, Multifocal breast carcinoma - HP:0001552, Barrel-shaped chest
Phenotypic similarity 0.306 to mouse mutant involving RAB33B.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0021191, increased bone mineral density of lumbar vertebrae
HP:0006625, Multifocal breast carcinoma - MP:0021191, increased bone mineral density of lumbar vertebrae
Proximity score 0.500 in interactome to SEC23B and phenotypic similarity 0.990 to ?Cowden syndrome 7 associated with SEC23B.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.500 in interactome to SEC23B and phenotypic similarity 0.245 to fish mutant of SEC23B.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0000916, ventral mandibular arch decreased size, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0000916, ventral mandibular arch decreased size, abnormal
Known diseases:
OMIM:615222 Smith-McCort dysplasia 2 - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.003 (p=5.9E-1)

Phenotype Score: 0.532

Variant Score: 0.224

Phenotype matches to diseases consistent with this MOI:
Phenotypic similarity 0.532 to OMIM:615222 Smith-McCort dysplasia 2
Variants contributing to score:
INTERGENIC_VARIANT SNV 4-139483761-G-T [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.400 CONTRIBUTING VARIANT
Transcripts:
RAB33B:ENST00000305626.6::
Pathogenicity Data:
Best Score: 0.399943
REMM: 0.400
Frequency Data:
No frequency data
DOWNSTREAM_GENE_VARIANT SNV 4-139481474-T-C [0/1] rs72726552
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.049 CONTRIBUTING VARIANT
Transcripts:
RAB33B:ENST00000305626.6::
Pathogenicity Data:
Best Score: 0.0770111
REMM: 0.077
Frequency Data:
UK10K: 0.8331%
gnomAD_G_AFR: 0.1568%
gnomAD_G_AMR: 0.4273%
gnomAD_G_NFE: 1.3073%
gnomAD_G_SAS: 0.2721%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.001 (p=7.3E-1)

Phenotype Score: 0.250

Variant Score: 0.400

No phenotype matches to diseases with this MOI.
Variants contributing to score:
INTERGENIC_VARIANT SNV 4-139483761-G-T [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.400 CONTRIBUTING VARIANT
Transcripts:
RAB33B:ENST00000305626.6::
Pathogenicity Data:
Best Score: 0.399943
REMM: 0.400
Frequency Data:
No frequency data
Other passed variants:
INTERGENIC_VARIANT INS 4-139447658-C-CT [1/1] rs887826088
Variant score: 0.081
Transcripts:
RAB33B:ENST00000305626.6::
Pathogenicity Data:
Best Score: 0.0809988
REMM: 0.081
Frequency Data:
No frequency data

CAV3

Exomiser Score: 0.003 (p=5.9E-1)

Phenotype Score: 0.501

Variant Score: 0.258

Phenotype matches:
Proximity score 0.501 in interactome to CACNA1C and phenotypic similarity 0.643 to Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures associated with CACNA1C.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Proximity score 0.501 in interactome to CACNA1C and phenotypic similarity 0.349 to mouse mutant of CACNA1C.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002759, abnormal caudal vertebrae morphology
HP:0006625, Multifocal breast carcinoma - MP:0002759, abnormal caudal vertebrae morphology
Proximity score 0.501 in interactome to CACNA1C and phenotypic similarity 0.255 to fish mutant of CACNA1C.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0001052, mandibular arch skeleton morphology, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0001052, mandibular arch skeleton morphology, abnormal
Known diseases:
OMIM:123320 Creatine phosphokinase, elevated serum - autosomal dominant
OMIM:192600 Cardiomyopathy, familial hypertrophic - autosomal dominant
OMIM:606072 Rippling muscle disease 2 - autosomal dominant
OMIM:611818 Long QT syndrome 9 - autosomal dominant
OMIM:614321 Myopathy, distal, Tateyama type - autosomal dominant
ORPHA:101016 Romano-Ward syndrome - autosomal dominant
ORPHA:206599 Isolated asymptomatic elevation of creatine phosphokinase - autosomal dominant
ORPHA:488650 Distal myopathy, Tateyama type - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.003 (p=5.9E-1)

Phenotype Score: 0.501

Variant Score: 0.258

No phenotype matches to diseases with this MOI.
Variants contributing to score:
INTERGENIC_VARIANT DEL 3-8725545-ATT-A [0/1] rs35989448
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.258 CONTRIBUTING VARIANT
Transcripts:
CAV3:ENST00000343849.3::
Pathogenicity Data:
Best Score: 0.257562
REMM: 0.258
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.001 (p=7.2E-1)

Phenotype Score: 0.251

Variant Score: 0.411

No phenotype matches to diseases with this MOI.
Variants contributing to score:
MISSENSE_VARIANT SNV 3-8745644-C-T [0/1] rs72546668
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:4, LB:7, B:9)
Variant score: 0.565 CONTRIBUTING VARIANT
Transcripts:
CAV3:ENST00000343849.3:c.233C>T:p.(Thr78Met)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.2248%
gnomAD_E_AFR: 0.3554%
gnomAD_E_AMR: 0.0939%
gnomAD_E_EAS: 0.0076%
gnomAD_E_NFE: 0.2575%
gnomAD_E_SAS: 0.0638%
gnomAD_G_AFR: 0.3367%
gnomAD_G_AMR: 0.1176%
gnomAD_G_NFE: 0.3293%
gnomAD_G_SAS: 0.0207%
INTERGENIC_VARIANT DEL 3-8725545-ATT-A [0/1] rs35989448
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.258 CONTRIBUTING VARIANT
Transcripts:
CAV3:ENST00000343849.3::
Pathogenicity Data:
Best Score: 0.257562
REMM: 0.258
Frequency Data:
No frequency data
Other passed variants:
INTERGENIC_VARIANT SNV 3-8717372-G-A [0/1] rs868223501
Variant score: 0.002
Transcripts:
CAV3:ENST00000343849.3::
Pathogenicity Data:
Best Score: 0.002
REMM: 0.002
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 3-8720275-C-T [0/1] rs189173367
Variant score: 0.001
Transcripts:
CAV3:ENST00000343849.3::
Pathogenicity Data:
Best Score: 0.00563175
REMM: 0.006
Frequency Data:
gnomAD_G_AFR: 0.3658%
gnomAD_G_AMR: 0.7655%
gnomAD_G_NFE: 1.8611%
gnomAD_G_SAS: 1.5340%
UPSTREAM_GENE_VARIANT SNV 3-8729278-T-C [0/1] rs73021965
Variant score: 0.001
Transcripts:
CAV3:ENST00000343849.3::
Pathogenicity Data:
Best Score: 0.00209286
REMM: 0.002
Frequency Data:
UK10K: 1.6662%
gnomAD_G_AFR: 0.4092%
gnomAD_G_AMR: 1.8502%
gnomAD_G_EAS: 0.0387%
gnomAD_G_NFE: 1.6750%
gnomAD_G_SAS: 1.3284%

TPP1

Exomiser Score: 0.003 (p=6.0E-1)

Phenotype Score: 0.505

Variant Score: 0.249

Phenotype matches:
Phenotypic similarity 0.246 to zebrafish mutant involving TPP1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0001965, mandibular arch skeleton decreased size, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0001965, mandibular arch skeleton decreased size, abnormal
Proximity score 0.505 in interactome to POT1 and phenotypic similarity 0.950 to Familial melanoma associated with POT1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0100013, Neoplasm of the breast
HP:0006625, Multifocal breast carcinoma - HP:0100013, Neoplasm of the breast
Known diseases:
OMIM:204500 Ceroid lipofuscinosis, neuronal, 2 - autosomal recessive
OMIM:609270 Spinocerebellar ataxia, autosomal recessive 7 - autosomal recessive
ORPHA:168486 Congenital neuronal ceroid lipofuscinosis - autosomal recessive
ORPHA:168491 Late infantile neuronal ceroid lipofuscinosis - autosomal recessive
ORPHA:284324 Childhood-onset autosomal recessive slowly progressive spinocerebellar ataxia - autosomal recessive
ORPHA:79262 Adult neuronal ceroid lipofuscinosis - autosomal dominant/recessive
ORPHA:79263 Infantile neuronal ceroid lipofuscinosis - autosomal recessive
ORPHA:79264 Juvenile neuronal ceroid lipofuscinosis - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.003 (p=6.0E-1)

Phenotype Score: 0.505

Variant Score: 0.249

No phenotype matches to diseases with this MOI.
Variants contributing to score:
UPSTREAM_GENE_VARIANT DEL 11-6620191-CT-C [0/1] rs1014447672
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.249 CONTRIBUTING VARIANT
Transcripts:
TPP1:ENST00000299427.12::
Pathogenicity Data:
Best Score: 0.25225
REMM: 0.252
Frequency Data:
gnomAD_G_AFR: 0.0386%
gnomAD_G_AMR: 0.0982%
gnomAD_G_NFE: 0.0397%
gnomAD_G_SAS: 0.0829%

RTN2

Exomiser Score: 0.003 (p=6.0E-1)

Phenotype Score: 0.503

Variant Score: 0.245

Phenotype matches:
Proximity score 0.503 in interactome to SLC25A46 and phenotypic similarity 0.643 to Neuropathy, hereditary motor and sensory, type VIB associated with SLC25A46.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Known diseases:
OMIM:604805 Spastic paraplegia 12, autosomal dominant - autosomal dominant
ORPHA:100993 Autosomal dominant spastic paraplegia type 12 - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.003 (p=6.0E-1)

Phenotype Score: 0.503

Variant Score: 0.245

No phenotype matches to diseases with this MOI.
Variants contributing to score:
UPSTREAM_GENE_VARIANT INS 19-45497741-T-TATAG [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.245 CONTRIBUTING VARIANT
Transcripts:
RTN2:ENST00000245923.9::
Pathogenicity Data:
Best Score: 0.245385
REMM: 0.245
Frequency Data:
No frequency data

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.000 (p=8.5E-1)

Phenotype Score: 0.252

Variant Score: 0.253

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT SNV 19-45493131-C-T [0/1] rs200214311
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.261 CONTRIBUTING VARIANT
Transcripts:
RTN2:ENST00000245923.9:c.1033+29G>A:p.(=)
Pathogenicity Data:
Best Score: 0.274027
REMM: 0.274
Frequency Data:
UK10K: 0.0529%
gnomAD_E_AFR: 0.0242%
gnomAD_E_AMR: 0.2917%
gnomAD_E_NFE: 0.0846%
gnomAD_E_SAS: 0.0337%
gnomAD_G_AFR: 0.0217%
gnomAD_G_AMR: 0.1895%
gnomAD_G_NFE: 0.1014%
gnomAD_G_SAS: 0.0414%
UPSTREAM_GENE_VARIANT INS 19-45497741-T-TATAG [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.245 CONTRIBUTING VARIANT
Transcripts:
RTN2:ENST00000245923.9::
Pathogenicity Data:
Best Score: 0.245385
REMM: 0.245
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT INS 19-45487032-C-CTTTTTTTTTT [0/1] rs34799041
Variant score: 0.024
Transcripts:
RTN2:ENST00000245923.9:c.1498-920_1498-919insAAAAAAAAAA:p.(=)
Pathogenicity Data:
Best Score: 0.0243917
REMM: 0.024
Frequency Data:
No frequency data

SNAP29

Exomiser Score: 0.003 (p=6.2E-1)

Phenotype Score: 0.503

Variant Score: 0.227

Phenotype matches:
Phenotypic similarity 0.321 to mouse mutant involving SNAP29.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0010123, increased bone mineral content
HP:0006625, Multifocal breast carcinoma - MP:0010123, increased bone mineral content
Proximity score 0.503 in interactome to VAMP7 and phenotypic similarity 0.614 to 46,XY partial gonadal dysgenesis associated with VAMP7.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Known diseases:
OMIM:609528 Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome - autosomal recessive
ORPHA:66631 CEDNIK syndrome - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.003 (p=6.2E-1)

Phenotype Score: 0.503

Variant Score: 0.227

No phenotype matches to diseases with this MOI.
Variants contributing to score:
INTERGENIC_VARIANT INS 22-20897980-G-GTTTTTTT [0/1] rs361804
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.237 CONTRIBUTING VARIANT
Transcripts:
SNAP29:ENST00000215730.12::
Pathogenicity Data:
Best Score: 0.289477
REMM: 0.289
Frequency Data:
gnomAD_G_AFR: 0.7016%
gnomAD_G_AMR: 0.6364%
gnomAD_G_NFE: 0.8506%
gnomAD_G_SAS: 0.3155%
CODING_TRANSCRIPT_INTRON_VARIANT INS 22-20872820-C-CTTT [0/1] rs361677
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.218 CONTRIBUTING VARIANT
Transcripts:
SNAP29:ENST00000215730.12:c.434+2287_434+2288insTTT:p.(=)
Pathogenicity Data:
Best Score: 0.217754
REMM: 0.218
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.000 (p=8.6E-1)

Phenotype Score: 0.251

Variant Score: 0.218

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 22-20872820-C-CTTT [0/1] rs361677
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.218 CONTRIBUTING VARIANT
Transcripts:
SNAP29:ENST00000215730.12:c.434+2287_434+2288insTTT:p.(=)
Pathogenicity Data:
Best Score: 0.217754
REMM: 0.218
Frequency Data:
No frequency data
Other passed variants:
CODING_TRANSCRIPT_INTRON_VARIANT INS 22-20872820-C-CTT [0/1] rs361677
Variant score: 0.218
Transcripts:
SNAP29:ENST00000215730.12:c.434+2287_434+2288insTT:p.(=)
Pathogenicity Data:
Best Score: 0.217754
REMM: 0.218
Frequency Data:
No frequency data
CODING_TRANSCRIPT_INTRON_VARIANT DEL 22-20874317-GAC-G [0/1] rs368789277
Variant score: 0.025
Transcripts:
SNAP29:ENST00000215730.12:c.434+3785_434+3786del:p.(=)
Pathogenicity Data:
Best Score: 0.146393
REMM: 0.146
Frequency Data:
gnomAD_G_AFR: 0.4214%
gnomAD_G_AMR: 1.9623%
gnomAD_G_EAS: 0.4664%
gnomAD_G_NFE: 0.2528%
gnomAD_G_SAS: 0.4881%

PURA

Exomiser Score: 0.002 (p=6.7E-1)

Phenotype Score: 0.251

Variant Score: 0.461

Phenotype matches:
Proximity score 0.503 in interactome to FMR1 and phenotypic similarity 0.614 to Xq27.3q28 duplication syndrome associated with FMR1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Proximity score 0.503 in interactome to FMR1 and phenotypic similarity 0.277 to fish mutant of FMR1.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0000122, notochord undulate, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0000122, notochord undulate, abnormal
Known diseases:
OMIM:616158 Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties - autosomal dominant
ORPHA:314655 Severe neonatal hypotonia-seizures-encephalopathy syndrome due to 5q31.3 microdeletion (CNV)
ORPHA:438216 PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome due to a point mutation - autosomal dominant
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.002 (p=6.7E-1)

Phenotype Score: 0.251

Variant Score: 0.461

No phenotype matches to diseases with this MOI.
Variants contributing to score:
DISRUPTIVE_INFRAME_INSERTION INS 5-140114310-T-TGGC [0/1] rs754074166
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:1, LB:4, B:1)
Variant score: 0.834 CONTRIBUTING VARIANT
Transcripts:
PURA:ENST00000331327.5:c.144_146dup:p.(Gly49dup)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
gnomAD_E_AFR: 0.0666%
gnomAD_E_AMR: 0.0376%
gnomAD_E_EAS: 0.0391%
gnomAD_E_NFE: 0.0495%
gnomAD_E_SAS: 0.0456%
gnomAD_G_AFR: 0.0426%
gnomAD_G_AMR: 0.0418%
gnomAD_G_EAS: 0.1271%
gnomAD_G_NFE: 0.0584%
gnomAD_G_SAS: 0.0459%
INTERGENIC_VARIANT SNV 5-140104190-A-G [0/1] rs957245046
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.087 CONTRIBUTING VARIANT
Transcripts:
PURA:ENST00000331327.5::
Pathogenicity Data:
Best Score: 0.0876897
REMM: 0.088
Frequency Data:
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0262%
gnomAD_G_NFE: 0.0279%
gnomAD_G_SAS: 0.0207%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.001 (p=7.6E-1)

Phenotype Score: 0.503

Variant Score: 0.087

No phenotype matches to diseases with this MOI.
Variants contributing to score:
INTERGENIC_VARIANT SNV 5-140104190-A-G [0/1] rs957245046
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.087 CONTRIBUTING VARIANT
Transcripts:
PURA:ENST00000331327.5::
Pathogenicity Data:
Best Score: 0.0876897
REMM: 0.088
Frequency Data:
gnomAD_G_AFR: 0.0048%
gnomAD_G_AMR: 0.0262%
gnomAD_G_NFE: 0.0279%
gnomAD_G_SAS: 0.0207%

RAB3GAP2

Exomiser Score: 0.001 (p=7.6E-1)

Phenotype Score: 0.580

Variant Score: 0.000

Phenotype matches:
Phenotypic similarity 0.580 to Martsolf syndrome 1 associated with RAB3GAP2.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0004405, Prominent nipples
HP:0006625, Multifocal breast carcinoma - HP:0004405, Prominent nipples
Proximity score 0.500 in interactome to CACNA1C and phenotypic similarity 0.643 to Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures associated with CACNA1C.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003186, Inverted nipples
HP:0006625, Multifocal breast carcinoma - HP:0003186, Inverted nipples
Proximity score 0.500 in interactome to CACNA1C and phenotypic similarity 0.349 to mouse mutant of CACNA1C.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002759, abnormal caudal vertebrae morphology
HP:0006625, Multifocal breast carcinoma - MP:0002759, abnormal caudal vertebrae morphology
Proximity score 0.500 in interactome to CACNA1C and phenotypic similarity 0.255 to fish mutant of CACNA1C.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - ZP:0001052, mandibular arch skeleton morphology, abnormal
HP:0006625, Multifocal breast carcinoma - ZP:0001052, mandibular arch skeleton morphology, abnormal
Known diseases - observed variants incompatible with mode of inheritance:
OMIM:212720 Martsolf syndrome 1 - autosomal recessive
OMIM:614225 Warburg micro syndrome 2 - autosomal recessive
ORPHA:1387 Cataract-intellectual disability-hypogonadism syndrome - autosomal recessive
ORPHA:2510 Micro syndrome - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.000 (p=9.3E-1)

Phenotype Score: 0.250

Variant Score: 0.005

No phenotype matches to diseases with this MOI.
Variants contributing to score:
CODING_TRANSCRIPT_INTRON_VARIANT INS 1-220163744-C-CATATAT [0/1] rs373160821
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.005 CONTRIBUTING VARIANT
Transcripts:
RAB3GAP2:ENST00000358951.7:c.3154+988_3154+989insATATAT:p.(=)
Pathogenicity Data:
Best Score: 0.00536627
REMM: 0.005
Frequency Data:
No frequency data

WDR36

Exomiser Score: 0.001 (p=7.8E-1)

Phenotype Score: 0.502

Variant Score: 0.065

Phenotype matches:
Proximity score 0.502 in interactome to DHX37 and phenotypic similarity 0.614 to 46,XY partial gonadal dysgenesis associated with DHX37.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000771, Gynecomastia
HP:0006625, Multifocal breast carcinoma - HP:0000771, Gynecomastia
Known diseases:
OMIM:609887 Glaucoma 1, open angle, G - unknown
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.001 (p=7.8E-1)

Phenotype Score: 0.502

Variant Score: 0.065

No phenotype matches to diseases with this MOI.
Variants contributing to score:
INTERGENIC_VARIANT INS 5-111145403-T-TTGTGTGTG [0/1] rs10670284
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.117 CONTRIBUTING VARIANT
Transcripts:
WDR36:ENST00000513710.4::
Pathogenicity Data:
Best Score: 0.657225
REMM: 0.657
Frequency Data:
gnomAD_G_AFR: 1.0185%
gnomAD_G_AMR: 1.5218%
gnomAD_G_EAS: 1.0840%
gnomAD_G_NFE: 1.9559%
gnomAD_G_SAS: 1.0856%
THREE_PRIME_UTR_EXON_VARIANT SNV 5-111128624-C-G [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.012 CONTRIBUTING VARIANT
Transcripts:
WDR36:ENST00000513710.4:c.*1741C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0118909
REMM: 0.012
Frequency Data:
No frequency data

AUTOSOMAL_DOMINANT

Exomiser Score: 0.000 (p=8.3E-1)

Phenotype Score: 0.502

Variant Score: 0.012

No phenotype matches to diseases with this MOI.
Variants contributing to score:
THREE_PRIME_UTR_EXON_VARIANT SNV 5-111128624-C-G [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.012 CONTRIBUTING VARIANT
Transcripts:
WDR36:ENST00000513710.4:c.*1741C>G:p.(=)
Pathogenicity Data:
Best Score: 0.0118909
REMM: 0.012
Frequency Data:
No frequency data
Other passed variants:
UPSTREAM_GENE_VARIANT SNV 5-111088623-C-G [1/1] rs1314310420
Variant score: 0.043
Transcripts:
WDR36:ENST00000513710.4::
Pathogenicity Data:
Best Score: 0.0431393
REMM: 0.043
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT SNV 5-111089049-G-A [1/1] rs1235603196
Variant score: 0.036
Transcripts:
WDR36:ENST00000513710.4::
Pathogenicity Data:
Best Score: 0.0361028
REMM: 0.036
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT SNV 5-111088580-T-A [1/1] rs771437198
Variant score: 0.030
Transcripts:
WDR36:ENST00000513710.4::
Pathogenicity Data:
Best Score: 0.0298976
REMM: 0.030
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT INS 5-111088582-C-CACCAATATATATATTTAGGATAT [1/1] rs762851931
Variant score: 0.029
Transcripts:
WDR36:ENST00000513710.4::
Pathogenicity Data:
Best Score: 0.028625
REMM: 0.029
Frequency Data:
No frequency data
INTERGENIC_VARIANT DEL 5-111139322-TC-T [0/1] rs1554110828
Variant score: 0.008
Transcripts:
WDR36:ENST00000513710.4::
Pathogenicity Data:
Best Score: 0.0101417
REMM: 0.010
Frequency Data:
gnomAD_G_AFR: 0.2280%
gnomAD_G_AMR: 0.6045%
gnomAD_G_NFE: 0.8859%
gnomAD_G_SAS: 0.0275%
UPSTREAM_GENE_VARIANT SNV 5-111088138-G-T [1/1] rs153282
Variant score: 0.003
Transcripts:
WDR36:ENST00000513710.4::
Pathogenicity Data:
Best Score: 0.00256944
REMM: 0.003
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT SNV 5-111088900-T-G [1/1] rs376592578
Variant score: 0.002
Transcripts:
WDR36:ENST00000513710.4::
Pathogenicity Data:
Best Score: 0.00196667
REMM: 0.002
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT SNV 5-111088917-C-G [1|1] rs368357173
Variant score: 0.002
Transcripts:
WDR36:ENST00000513710.4::
Pathogenicity Data:
Best Score: 0.00196667
REMM: 0.002
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT SNV 5-111088885-C-T [1|1] rs13166760
Variant score: 0.002
Transcripts:
WDR36:ENST00000513710.4::
Pathogenicity Data:
Best Score: 0.00176667
REMM: 0.002
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT SNV 5-111088886-A-G [1|1] rs372027239
Variant score: 0.002
Transcripts:
WDR36:ENST00000513710.4::
Pathogenicity Data:
Best Score: 0.00176667
REMM: 0.002
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT SNV 5-111088920-C-A [1|1] rs13166897
Variant score: 0.001
Transcripts:
WDR36:ENST00000513710.4::
Pathogenicity Data:
Best Score: 9.66667E-4
REMM: 0.001
Frequency Data:
No frequency data
UPSTREAM_GENE_VARIANT SNV 5-111090743-G-A [0/1] rs2126621154
Variant score: 0.000
Transcripts:
WDR36:ENST00000513710.4::
Pathogenicity Data:
Best Score: 6.0E-4
REMM: 0.001
Frequency Data:
gnomAD_G_AFR: 0.5229%
gnomAD_G_AMR: 0.7520%
gnomAD_G_NFE: 0.9925%
gnomAD_G_SAS: 0.1663%

SLX4

Exomiser Score: 0.001 (p=7.9E-1)

Phenotype Score: 0.506

Variant Score: 0.051

Phenotype matches:
Phenotypic similarity 0.348 to mouse mutant involving SLX4.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0004174, abnormal spine curvature
HP:0006625, Multifocal breast carcinoma - MP:0004174, abnormal spine curvature
Proximity score 0.506 in interactome to TERF2IP and phenotypic similarity 0.950 to Familial melanoma associated with TERF2IP.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0100013, Neoplasm of the breast
HP:0006625, Multifocal breast carcinoma - HP:0100013, Neoplasm of the breast
Known diseases:
OMIM:613951 Fanconi anemia, complementation group P - autosomal recessive
ORPHA:84 Fanconi anemia - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.001 (p=7.9E-1)

Phenotype Score: 0.506

Variant Score: 0.051

No phenotype matches to diseases with this MOI.
Variants contributing to score:
SYNONYMOUS_VARIANT SNV 16-3590449-G-A [0/1] rs200742809
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:1, LB:5)
Variant score: 0.099 CONTRIBUTING VARIANT
Transcripts:
SLX4:ENST00000294008.4:c.3189C>T:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.0397%
gnomAD_E_AFR: 0.0060%
gnomAD_E_AMR: 0.0268%
gnomAD_E_EAS: 0.0050%
gnomAD_E_NFE: 0.0309%
gnomAD_E_SAS: 0.0336%
gnomAD_G_AFR: 0.0144%
gnomAD_G_AMR: 0.0980%
gnomAD_G_NFE: 0.0485%
CODING_TRANSCRIPT_INTRON_VARIANT SNV 16-3598581-G-A [0/1] rs573564774
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.002 CONTRIBUTING VARIANT
Transcripts:
SLX4:ENST00000294008.4:c.1164-582C>T:p.(=)
Pathogenicity Data:
Best Score: 0.00247619
REMM: 0.002
Frequency Data:
UK10K: 0.0264%
gnomAD_G_AFR: 0.0313%
gnomAD_G_AMR: 0.0980%
gnomAD_G_NFE: 0.0500%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.000 (p=9.0E-1)

Phenotype Score: 0.253

Variant Score: 0.099

No phenotype matches to diseases with this MOI.
Variants contributing to score:
SYNONYMOUS_VARIANT SNV 16-3590449-G-A [0/1] rs200742809
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
ClinVar: CONFLICTING_PATHOGENICITY_INTERPRETATIONS (CRITERIA_PROVIDED_CONFLICTING_INTERPRETATIONS) (VUS:1, LB:5)
Variant score: 0.099 CONTRIBUTING VARIANT
Transcripts:
SLX4:ENST00000294008.4:c.3189C>T:p.(=)
Pathogenicity Data:
No pathogenicity data
Frequency Data:
UK10K: 0.0397%
gnomAD_E_AFR: 0.0060%
gnomAD_E_AMR: 0.0268%
gnomAD_E_EAS: 0.0050%
gnomAD_E_NFE: 0.0309%
gnomAD_E_SAS: 0.0336%
gnomAD_G_AFR: 0.0144%
gnomAD_G_AMR: 0.0980%
gnomAD_G_NFE: 0.0485%

PCK1

Exomiser Score: 0.001 (p=7.9E-1)

Phenotype Score: 0.504

Variant Score: 0.049

Phenotype matches:
Proximity score 0.504 in interactome to DUSP6 and phenotypic similarity 0.620 to Kallmann syndrome associated with DUSP6.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003187, Breast hypoplasia
HP:0006625, Multifocal breast carcinoma - HP:0003187, Breast hypoplasia
Proximity score 0.504 in interactome to DUSP6 and phenotypic similarity 0.324 to mouse mutant of DUSP6.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0000438, abnormal cranium morphology
HP:0006625, Multifocal breast carcinoma - MP:0000438, abnormal cranium morphology
Known diseases:
OMIM:261680 Phosphoenolpyruvate carboxykinase deficiency, cytosolic - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_RECESSIVE

Exomiser Score: 0.001 (p=7.9E-1)

Phenotype Score: 0.504

Variant Score: 0.049

No phenotype matches to diseases with this MOI.
Variants contributing to score:
INTERGENIC_VARIANT DEL 20-57550771-CAAAA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.085 CONTRIBUTING VARIANT
Transcripts:
PCK1:ENST00000319441.6::
Pathogenicity Data:
Best Score: 0.0847246
REMM: 0.085
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 20-57555522-C-T [0/1] rs118015275
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE []
Variant score: 0.013 CONTRIBUTING VARIANT
Transcripts:
PCK1:ENST00000319441.6::
Pathogenicity Data:
Best Score: 0.0191063
REMM: 0.019
Frequency Data:
UK10K: 0.8331%
gnomAD_G_AFR: 0.1708%
gnomAD_G_AMR: 0.5427%
gnomAD_G_NFE: 0.9880%
gnomAD_G_SAS: 1.2023%

AUTOSOMAL_DOMINANT

Exomiser Score: 0.000 (p=9.0E-1)

Phenotype Score: 0.252

Variant Score: 0.085

No phenotype matches to diseases with this MOI.
Variants contributing to score:
INTERGENIC_VARIANT DEL 20-57550771-CAAAA-C [0/1]
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.085 CONTRIBUTING VARIANT
Transcripts:
PCK1:ENST00000319441.6::
Pathogenicity Data:
Best Score: 0.0847246
REMM: 0.085
Frequency Data:
No frequency data
Other passed variants:
INTERGENIC_VARIANT SNV 20-57579299-T-C [1/1]
Variant score: 0.040
Transcripts:
PCK1:ENST00000319441.6::
Pathogenicity Data:
Best Score: 0.0401397
REMM: 0.040
Frequency Data:
No frequency data
INTERGENIC_VARIANT SNV 20-57585092-G-A [0/1] rs143491982
Variant score: 0.000
Transcripts:
PCK1:ENST00000319441.6::
Pathogenicity Data:
Best Score: 4.11111E-4
REMM: 0.000
Frequency Data:
UK10K: 0.3306%
gnomAD_G_AFR: 0.0724%
gnomAD_G_AMR: 0.2746%
gnomAD_G_NFE: 0.3781%
gnomAD_G_SAS: 0.1039%

AGA

Exomiser Score: 0.000 (p=8.4E-1)

Phenotype Score: 0.501

Variant Score: 0.000

Phenotype matches:
Phenotypic similarity 0.465 to Aspartylglucosaminuria associated with AGA.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0000768, Pectus carinatum
HP:0006625, Multifocal breast carcinoma - HP:0000768, Pectus carinatum
Proximity score 0.501 in interactome to ATM and phenotypic similarity 0.998 to Breast cancer, susceptibility to associated with ATM.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - HP:0003002, Breast carcinoma
HP:0006625, Multifocal breast carcinoma - HP:0003002, Breast carcinoma
Proximity score 0.501 in interactome to ATM and phenotypic similarity 0.207 to mouse mutant of ATM.
Best Phenotype Matches:
HP:0003002, Breast carcinoma - MP:0002145, abnormal T cell differentiation
HP:0006625, Multifocal breast carcinoma - MP:0002145, abnormal T cell differentiation
Known diseases - observed variants incompatible with mode of inheritance:
OMIM:208400 Aspartylglucosaminuria - autosomal recessive
ORPHA:93 Aspartylglucosaminuria - autosomal recessive
Gene scores under compatible inheritance modes:

AUTOSOMAL_DOMINANT

Exomiser Score: 0.000 (p=8.7E-1)

Phenotype Score: 0.251

Variant Score: 0.201

No phenotype matches to diseases with this MOI.
Variants contributing to score:
REGULATORY_REGION_VARIANT DEL 4-181309467-TTTTTTTTTTTG-T [0/1] rs1221142812
Exomiser ACMG: UNCERTAIN_SIGNIFICANCE [PM2_Supporting]
Variant score: 0.201 CONTRIBUTING VARIANT
Transcripts:
AGA:ENST00000264595.7::
AGA:ENST00000511685.6::
Pathogenicity Data:
Best Score: 0.201229
REMM: 0.201
Frequency Data:
No frequency data

Unanalysed Variants

REGULATORY_REGION_VARIANT 2-232512865-C-T [0/1] rs11687197
REGULATORY_REGION_VARIANT 3-115793141-G-A [0/1] rs555727987
REGULATORY_REGION_VARIANT 16-46758007-C-T [0/1] rs113682715
REGULATORY_REGION_VARIANT 16-48057430-T-C [0/1] rs527920999
REGULATORY_REGION_VARIANT 19-7674571-G-A [0/1]

About

The Exomizer is a Java program that functionally annotates variants from whole-exome sequencing data starting from a VCF file (version 4). The functional annotation code is based on Jannovar and uses UCSC KnownGene transcript definitions and hg19 genomic coordinates

Variants are prioritized according to user-defined criteria on variant frequency, pathogenicity, quality, inheritance pattern, and model organism phenotype data. Predicted pathogenicity data was extracted from the dbNSFP resource.

Developed by the Computational Biology and Bioinformatics group at the Institute for Medical Genetics and Human Genetics of the Charité - Universitätsmedizin Berlin, the Mouse Informatics Group at the Sanger Institute and the Smedley group at Queen Mary University of London.

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